Download and practice these free 300-100 real questions.

killexams.com is a trustworthy and true stage who furnishes 300-100 braindumps with 100 percent pass ensure. You really want to rehearse 300-100 inquiries for at least 24 hours to score appropriately in the 300-100 test. Your real excursion to finish in LPIC-3 Exam 300: Mixed Environments- version 1.0 test, certainly begins with killexams.com 300-100 braindumps.

Exam Code: 300-100 Practice exam 2023 by Killexams.com team
300-100 LPIC-3 exam 300: Mixed Environments, version 1.0

Exam Title : LPIC-3 Mixed Environment
Exam ID : 300-100
Exam Duration : 90 mins
Questions in exam : 60
Passing Score : 500 / 800
Exam Center : LPI Marketplace
Real Questions : LPI LPIC-3 Real Questions
VCE VCE exam : LPI 300-100 Certification VCE Practice Test

Topic 390: OpenLDAP Configuration
390.1 OpenLDAP Replication
Description: Candidates should be familiar with the server replication available with OpenLDAP.
Key Knowledge Areas:
- Replication concepts
- Configure OpenLDAP replication
- Analyze replication log files
- Understand replica hubs
- LDAP referrals
- LDAP sync replication
The following is a partial list of the used files, terms and utilities:
- master / slave server
- multi-master replication
- consumer
- replica hub
- one-shot mode
- referral
- syncrepl
- pull-based / push-based synchronization
- refreshOnly and refreshAndPersist
- replog
390.2 Securing the Directory
Weight: 3
Description: Candidates should be able to configure encrypted access to the LDAP directory, and restrict access at the firewall level.
Key Knowledge Areas:
- Securing the directory with SSL and TLS
- Firewall considerations
- Unauthenticated access methods
- User / password authentication methods
- Maintanence of SASL user DB
- Client / server certificates
Terms and Utilities:
- SSL / TLS
- Security Strength Factors (SSF)
- SASL
- proxy authorization
- StartTLS
- iptables
390.3 OpenLDAP Server Performance Tuning
Weight: 2
Description: Candidates should be capable of measuring the performance of an LDAP server, and tuning configuration directives.
Key Knowledge Areas:
- Measure OpenLDAP performance
- Tune software configuration to increase performance
- Understand indexes
Terms and Utilities:
- index
- DB_CONFIG
Topic 391: OpenLDAP as an Authentication Backend
391.1 LDAP Integration with PAM and NSS
Weight: 2
Description: Candidates should be able to configure PAM and NSS to retrieve information from an LDAP directory.
Key Knowledge Areas:
- Configure PAM to use LDAP for authentication
- Configure NSS to retrieve information from LDAP
- Configure PAM modules in various Unix environments
Terms and Utilities:
- PAM
- NSS
- /etc/pam.d/
- /etc/nsswitch.conf
391.2 Integrating LDAP with Active Directory and Kerberos
Weight: 2
Description: Candidates should be able to integrate LDAP with Active Directory Services.
Key Knowledge Areas:
- Kerberos integration with LDAP
- Cross platform authentication
- Single sign-on concepts
- Integration and compatibility limitations between OpenLDAP and Active Directory
Terms and Utilities:
- Kerberos
- Active Directory
- single sign-on
- DNS
Topic 392: Samba Basics
392.1 Samba Concepts and Architecture
Weight: 2
Description: Candidates should understand the essential concepts of Samba. As well, the major differences between Samba3 and Samba4 should be known.
Key Knowledge Areas:
- Understand the roles of the Samba daemons and components
- Understand key issues regarding heterogeneous networks
- Identify key TCP/UDP ports used with SMB/CIFS
- Knowledge of Samba3 and Samba4 differences
The following is a partial list of the used files, terms and utilities:
- /etc/services
- Samba daemons: smbd, nmbd, samba, winbindd
392.2 Configure Samba
Weight: 4
Description: Candidates should be able to configure the Samba daemons for a wide variety of purposes.
Key Knowledge Areas:
- Knowledge of Samba server configuration file structure
- Knowledge of Samba variables and configuration parameters
- Troubleshoot and debug configuration problems with Samba
Terms and Utilities:
- smb.conf
- smb.conf parameters
- smb.conf variables
- testparm
- secrets.tdb
392.3 Regular Samba Maintenance
Weight: 2
Description: Candidates should know about the various tools and utilities that are part of a Samba installation.
Key Knowledge Areas:
- Monitor and interact with running Samba daemons
- Perform regular backups of Samba configuration and state data Terms and Utilities:
- smbcontrol
- smbstatus
- tdbbackup
392.4 Troubleshooting Samba
Weight: 2
Description: Candidates should understand the structure of trivial database files and know how troubleshoot problems.
Key Knowledge Areas:
- Configure Samba logging
- Backup TDB files
- Restore TDB files
- Identify TDB file corruption
- Edit / list TDB file content
Terms and Utilities:
- /var/log/samba/
- log level
- debuglevel
- smbpasswd
- pdbedit
- secrets.tdb
- tdbbackup
- tdbdump
- tdbrestore
- tdbtool
392.5 Internationalization
Weight: 1
Description: Candidates should be able to work with internationalization character codes and code pages.
Key Knowledge Areas:
- Understand internationalization character codes and code pages
- Understand the difference in the name space between Windows and Linux/Unix with respect to share, file and directory names in a non-English environment
- Understand the difference in the name space between Windows and Linux/Unix with respect to user and group naming in a non-English environment
- Understand the difference in the name space between Windows and Linux/Unix with respect to computer naming in a non-English environment
Terms and Utilities:
- internationalization
- character codes
- code pages
- smb.conf
- dos charset, display charset and unix charset
Topic 393: Samba Share Configuration
393.1 File Services
Weight: 4
Description: Candidates should be able to create and configure file shares in a mixed environment.
Key Knowledge Areas:
- Create and configure file sharing
- Plan file service migration
- Limit access to IPC$
- Create scripts for user and group handling of file shares
- Samba share access configuration parameters
Terms and Utilities:
- smb.conf
- [homes]
- smbcquotas
- smbsh
- browseable, writeable, valid users, write list, read list, read only and guest ok
- IPC$
- mount, smbmount
393.2 Linux File System and Share/Service Permissions
Weight: 3
Description: Candidates should understand file permissions on a Linux file system in a mixed environment.
Key Knowledge Areas:
- Knowledge of file / directory permission control
- Understand how Samba interacts with Linux file system permissions and ACLs
- Use Samba VFS to store Windows ACLs
Terms and Utilities:
- smb.conf
- chmod, chown
- create mask, directory mask, force create mode, force directory mode
- smbcacls
- getfacl, setfacl
- vfs_acl_xattr, vfs_acl_tdb and vfs objects
393.3 Print Services
Weight: 2
Description: Candidates should be able to create and manage print shares in a mixed environment.
Key Knowledge Areas:
- Create and configure printer sharing
- Configure integration between Samba and CUPS
- Manage Windows print drivers and configure downloading of print drivers
- Configure [print$]
- Understand security concerns with printer sharing
- Uploading printer drivers for Point’n’Print driver installation using ‘Add Print Driver Wizard’ in Windows
Terms and Utilities:
- smb.conf
- [print$]
- CUPS
- cupsd.conf
- /var/spool/samba/.
- smbspool
- rpcclient
- net Topic 394: Samba User and Group Management
394.1 Managing User Accounts and Groups
Weight: 4
Description: Candidates should be able to manage user and group accounts in a mixed environment.
Key Knowledge Areas:
- Manager user and group accounts
- Understand user and group mapping
- Knowledge of user account management tools
- Use of the smbpasswd program
- Force ownership of file and directory objects
Terms and Utilities:
- pdbedit
- smb.conf
- samba-tool user (with subcommands)
- samba-tool group (with subcommands)
- smbpasswd
- /etc/passwd
- /etc/group
- force user, force group.
- idmap
394.2 Authentication, Authorization and Winbind
Weight: 5
Description: Candidates should understand the various authentication mechanisms and configure access control. Candidates should be able to install and configure the Winbind service.
Key Knowledge Areas:
- Setup a local password database
- Perform password synchronization
- Knowledge of different passdb backends
- Convert between Samba passdb backends
- Integrate Samba with LDAP
- Configure Winbind service
- Configure PAM and NSS
Terms and Utilities:
- smb.conf
- smbpasswd, tdbsam, ldapsam
- passdb backend
- libnss_winbind
- libpam_winbind
- libpam_smbpass
- wbinfo
- getent
- SID and foreign SID
- /etc/passwd
- /etc/group
Topic 395: Samba Domain Integration
395.1 Samba as a PDC and BDC
Weight: 3
Description: Candidates should be able to setup and maintain primary and backup domain controllers. Candidates should be able to manage Windows/Linux client access to the NT-Style domains.
Key Knowledge Areas:
- Understand and configure domain membership and trust relationships
- Create and maintain a primary domain controller with Samba3 and Samba4
- Create and maintain a backup domain controller with Samba3 and Samba4
- Add computers to an existing domain
- Configure logon scripts
- Configure roaming profiles
- Configure system policies
Terms and Utilities:
- smb.conf
- security mode
- server role
- domain logons
- domain master
- logon script
- logon path
- NTConfig.pol
- net
- profiles
- add machine script
- profile acls
395.2 Samba4 as an AD compatible Domain Controller
Weight: 3
Description: Candidates should be able to configure Samba 4 as an AD Domain Controller.
Key Knowledge Areas:
- Configure and test Samba 4 as an AD DC
- Using smbclient to confirm AD operation
- Understand how Samba integrates with AD services: DNS, Kerberos, NTP, LDAP
Terms and Utilities:
- smb.conf
- server role
- samba-tool domain (with subcommands)
- samba
395.3 Configure Samba as a Domain Member Server
Weight: 3
Description: Candidates should be able to integrate Linux servers into an environment where Active Directory is present.
Key Knowledge Areas:
- Joining Samba to an existing NT4 domain
- Joining Samba to an existing AD domain
- Ability to obtain a TGT from a KDC
Terms and Utilities:
- smb.conf
- server role
- server security
- net command
- kinit, TGT and REALM
Topic 396: Samba Name Services
396.1 NetBIOS and WINS
Weight: 3
Description: Candidates should be familiar with NetBIOS/WINS concepts and understand network browsing.
Key Knowledge Areas:
- Understand WINS concepts
- Understand NetBIOS concepts
- Understand the role of a local master browser
- Understand the role of a domain master browser
- Understand the role of Samba as a WINS server
- Understand name resolution
- Configure Samba as a WINS server
- Configure WINS replication
- Understand NetBIOS browsing and browser elections
- Understand NETBIOS name types
Terms and Utilities:
- smb.conf
- nmblookup
- smbclient
- name resolve order
- lmhosts
- wins support, wins server, wins proxy, dns proxy
- domain master, os level, preferred master
396.2 Active Directory Name Resolution
Weight: 2
Description: Candidates should be familiar with the internal DNS server with Samba4.
Key Knowledge Areas:
- Understand and manage DNS for Samba4 as an AD Domain Controller
- DNS forwarding with the internal DNS server of Samba4
Terms and Utilities:
- samba-tool dns (with subcommands)
- smb.conf
- dns forwarder
- /etc/resolv.conf
- dig, host
Topic 397: Working with Linux and Windows Clients
397.1 CIFS Integration
Weight: 3
Description: Candidates should be comfortable working with CIFS in a mixed environment.
Key Knowledge Areas:
- Understand SMB/CIFS concepts
- Access and mount remote CIFS shares from a Linux client
- Securely storing CIFS credentials
- Understand features and benefits of CIFS
- Understand permissions and file ownership of remote CIFS shares
Terms and Utilities:
- SMB/CIFS
- mount, mount.cifs
- smbclient
- smbget
- smbtar
- smbtree
- findsmb
- smb.conf
- smbcquotas
- /etc/fstab
397.2 Working with Windows Clients
Weight: 2
Description: Candidates should be able to interact with remote Windows clients, and configure Windows workstations to access file and print services from Linux servers.
Key Knowledge Areas:
- Knowledge of Windows clients
- Explore browse lists and SMB clients from Windows
- Share file / print resources from Windows
- Use of the smbclient program
- Use of the Windows net utility
Terms and Utilities:
- Windows net command
- smbclient
- control panel
- rdesktop
- workgroup

LPIC-3 exam 300: Mixed Environments, version 1.0
LPI Environments, Topics
Killexams : LPI Environments, courses - BingNews https://killexams.com/pass4sure/exam-detail/300-100 Search results Killexams : LPI Environments, courses - BingNews https://killexams.com/pass4sure/exam-detail/300-100 https://killexams.com/exam_list/LPI Killexams : LPI confident of tackling challenges in 2023

KUALA LUMPUR: LPI Capital Bhd said it will remain focused on business growth to offset an expected compression in margins following the implementation of Phase 2A of the market liberalisation plan.

Presenting its outlook for 2023, the insurer said it remains confident of its ability to adapt and innovate despite the insurance industry facing rising claims and reinsurance costs.

It noted also the global political and economic uncertainties and rapidly changing operating models.

"The LPI Group’s prudent underwriting approach and diversified business development channels will facilitate it to weather the numerous challenges in FY2023," it added in a statement.

In the fourth quarter of FY22 ended Dec 31, 2022, LPI said net profit was RM83.57mil, 14.47% improved from RM73.07mil in the previous corresponding quarter.

This came on the back of revenue of RM433.17mil in 4QFY22, up from RM429.04mil in 4QFY21.

According to the group, the improved quarterly performance was mainly contributed by an increase in investment income and a lower provision for fair value losses on investment.

For the full year, LPI's net profit came to RM276.61mil, down from RM344.68mil a year earlier.

The company's earnings per share dropped to 69.43 sen FY22 as compared with 86.52 sen in FY21.

The company reported revenue of RM1.66bil for the year under review, 3.5% lower from RM1.72bil in FY21.

The group announced a second interim dividend of 35 sen per share amounting to RM139.4mil despite the lower profitability in FY22.

This brings LPI's total dividend payout in FY22 to 60 sen a share or RM239mil, representing 86.4% of the group's net profit attributable to shareholders.

"In FY2022, the group’s performance was affected by significant changes to the operating environment as the domestic economy reopened following two years of pandemic-related restrictions under the Movement Control Order (MCO).

"While the resumption of business and social activities catalysed a return to growth, it also gave rise to insurance claims returning to pre-pandemic level following a significant decline over the past two years," said LPI.

It said its wholly owned subsidiary Lonpac Insurance Bhd continued to see an increase in claims frequency and value with its claims incurred ratio deteriorating to 40.5% from 37.7% in the previous corresponding quarter.

"With management expense ratio at 18% and commission ratio at 7.6%, Lonpac’s combined ratio for the 4th quarter of FY22 rose to 66.1% against 62.8% reported in the previous corresponding Quarter.

"With the higher claims experience, the Underwriting Profit of Lonpac was 4.5% lower at RM91mil against RM95.3mil achieved in FY2021," said LPI.

Mon, 06 Feb 2023 15:21:00 -0600 en text/html https://www.thestar.com.my/business/business-news/2023/02/07/lpi-confident-of-tackling-challenges-in-2023
Killexams : LPI prepares for challenging outlook

“The LPI Group will remain focused on business growth to offset the expected compression in margins arising from the implementation of phase 2A of the market liberalisation plan,” the company said.

PETALING JAYA: LPI Capital Bhd expects a more challenging outlook for the year and will adapt to face the circumstances ahead.

The insurer said it remained confident of its ability to adapt and innovate.

“The LPI Group will remain focused on business growth to offset the expected compression in margins arising from the implementation of phase 2A of the market liberalisation plan,” the company said in a statement.

“We will continue to drive our digital transformation to Boost the customer experience and enhance operational efficiency.

“The LPI Group’s prudent underwriting approach and diversified business development channels will facilitate it to weather the numerous challenges in 2023,” it added.

According to the group, the country’s economy is expected to moderate in 2023 amid challenging external conditions and slowing domestic demand.

“As the insurance industry faces rising claims and reinsurance costs, global political and economic uncertainties and rapidly changing operating models, the ability to change and effectively adapt quickly remains as important as ever.

“We will also continue to drive our digital transformation to Boost the customer experience and enhance operational efficiency.

LPI Capital’s fourth quarter ended Dec 31, 2022 net profit showed a 14.4% year-on-year (y-o-y) improvement to RM83.57mil on the back of quarterly revenues improving by 1% y-o-y to RM429mil.

“The improved profitability was mainly contributed by an increase in investment income and a lower provision for fair value losses on investment,” it said.

LPI said its net return on equity for the same period under review was higher at 3.8% from 3.4% while earnings per share came in at 20.97 sen compared with 18.34 sen recorded in the previous year’s corresponding quarter.LPI Capital had declared a second interim single-tier dividend of 35 sen that would be paid on March 2.

The group said the entitlement would be determined on the basis of the record of depositors as at Feb 22, 2023.

In FY22, LPI Capital said its performance was affected by significant changes in the operating environment as the domestic economy reopened after the Covid-19 lockdowns.

“While the resumption of business and social activities catalysed a return to growth, it also gave rise to insurance claims returning to pre-pandemic level following a significant decline over the past two years,” it said.

“As a result of the normalisation of claims, the group’s profitability had deteriorated on a year-on-year basis,” it added.

Tue, 07 Feb 2023 12:22:00 -0600 en text/html https://www.thestar.com.my/business/business-news/2023/02/08/lpi-prepares-for-challenging-outlook
Killexams : How Cannabis Compound Counters Epileptic Seizures

the work confirmed a previous finding that CBD blocks the ability of LPI to amplify nerve signals in a brain region called the hippocampus. The current findings argue for the first time that LPI also weakens signals that counter seizures, further explaining the value of CBD treatment.

"Our results deepen the field's understanding of a central seizure-inducing mechanism, with many implications for the pursuit of new treatment approaches," said corresponding author Richard W. Tsien, chair of the Department of Physiology and Neuroscience at NYU Langone Health.

Advertisement


"Related imbalances are present in autism and schizophrenia, so the paper may have a broader impact." The study results build on how each neuron "fires" to send an electrical pulse down an extension of itself until it reaches a synapse, the gap that connects it to the next cell in a neuronal pathway. When it reaches the cell's end before the synapse, the pulse triggers the release of compounds called neurotransmitters that float across the gap to affect the next cell in line. Upon crossing, such signals either encourage the cell to fire (excitation), or apply the brakes on firing (inhibition). Balance between the two are essential to brain function; too much excitation promotes seizures.

The new study looked at several rodent models to explore mechanisms behind seizures, often by measuring information-carrying electrical current flows with fine-tipped electrodes. Other experiments looked at the effect of LPI by genetically removing its main signaling partner, or by measuring the release of LPI following seizures.

The tests confirmed past findings that LPI influences nerve signals by binding to a protein called G-coupled receptor 55 (GPR55), on neuron cell surfaces. This LPI-GPR55 presynaptic interaction was found to cause the release of calcium ions within the cell, which encouraged cells to release glutamate, the main excitatory neurotransmitter. Further, when LPI activated GPR55 on the other side of the synapse, it weakened inhibition, by decreasing the supply and proper arrangement of proteins necessary for inhibition. Collectively, this creates a "dangerous" two-pronged mechanism to increase excitability, say the authors.

While prior studies had implicated GPR55 as a seizure-reducing target of CBD, the current work provided a more detailed, proposed mechanism of action.

The authors propose that CBD blocks a "positive feedback loop" in which seizures increase LPI-GPR55 signaling, which likely encourages more seizures, which in turn increases levels of both LPI and GPR55. The proposed vicious cycle provides one process that could explain repeated epileptic seizures, although future studies are needed to confirm this.

Further, the current study examined the plant-based cannabinoid CBD, but the authors note that LPI is part of signaling network that includes "endocannabinoids" like 2-Arachidonoylglycerol (2-AG) that occur naturally in human tissues. LPI and 2-AG target receptors also regulated by CBD, but have different actions at the synapse. While LPI amplifies incoming electrical signals, endocannabinoids like 2-AG respond to increases in brain activity by dialing down the release of neurotransmitters from nerve cells. Interestingly, LPI and 2-AG can be converted into each other through actions of enzymes.

"Theoretically, the brain could control activity by toggling between pro-excitatory LPI and the restorative actions of 2-AG," said first study author Evan Rosenberg, PhD, a post-doctoral scholar in the Tsein's lab. "Drug designers could inhibit the enzymes that underpin LPI production or promote its conversion to 2-AG, as an additional approach to control seizures. LPI could also serve as a biomarker of seizures or predictor of clinical responsiveness to CBD, providing an area of future research."

Source: Eurekalert

Mon, 13 Feb 2023 09:32:00 -0600 en-US text/html https://www.medindia.net/news/how-cannabis-compound-counters-epileptic-seizures-210468-1.htm
Killexams : CBD Counters Hippocampal Hyperactivity in Epilepsy

A study by researchers in the U.S. and U.K. has revealed a previously unknown mechanism by which cannabidiol (CBD)—a non-psychoactive component of cannabis—reduces seizures in many treatment-resistant forms of pediatric epilepsy. Led by researchers at NYU Grossman School of Medicine, the new study, in rodent models, found that CBD blocked signals carried by a molecule called lysophosphatidylinositol (LPI) in neurons. LPI is thought to amplify nerve signals as part of normal function, but can be hijacked by disease to promote seizures.

The new research confirmed a previous finding that CBD blocks the ability of LPI to amplify nerve signals in the brain’s hippocampus, and argues for the first time that LPI also weakens signals that counter seizures, further explaining the value of CBD treatment.

“Our results deepen the field’s understanding of a central seizure-inducing mechanism, with many implications for the pursuit of new treatment approaches,” said corresponding author Richard W. Tsien, PhD, chair of the Department of Physiology and Neuroscience at NYU Langone Health. “The study also clarified, not just how CBD counters seizures, but more broadly how circuits are balanced in the brain. Related imbalances are present in autism and schizophrenia, so the paper may have a broader impact.”

Tsein, together with colleagues at NYU Langone, and collaborators in the U.S. and U.K., reported on their work in Neuron, in a paper titled “Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity.”

When a neuron “fires” it sends an electrical pulse down an extension of itself until it reaches a synapse, the gap that connects one neuron to the next cell in a neuronal pathway. When the electrical impulse reaches the cell’s end before the synapse, it triggers the release of neurotransmitters that are travel across the gap to reach the next cell. Upon crossing this synapse, such signals either encourage the next cell to fire (excitation), or apply the brakes on firing (inhibition). Balance between the two are essential to brain function; too much excitation promotes seizures, and an imbalance between inhibition and excitation is also implicated in other disorders. “Neuronal circuits require coordination between synaptic excitation (E) and inhibition (I) for proper function,” the authors wrote, ”and disruptions in the excitatory-to-inhibitory (E:I) ratio contribute to epilepsy, autism spectrum disorders, and schizophrenia.”

But while cannabidiol has been shown to reduce seizures in multiple forms of pediatric epilepsies, the mechanism(s) of anti-seizure action remain unclear. “In preclinical models, CBD reduces spontaneous recurrent seizures and regulates the E:I ratio in acute seizures; however, the molecular signaling underlying CBD’s anti-seizure actions remains poorly defined.”

Possible therapeutic targets of CBD encompass ion channels, transporters, and transmembrane signaling proteins, the team noted. Among the proposed candidates are two GPCRs: the cannabinoid receptor CB1R and the receptor GPR55.  “In one model, CBD acts at glutamatergic axon terminals, blocking the pro-excitatory actions of the endogenous membrane phospholipid lysophosphatidylinositol, at the G-protein-coupled receptor GPR55 … However, the impact of LPI-GPR55 signaling at inhibitory synapses and in epileptogenesis remains underexplored.”

For their new study, the team looked at several rodent models to explore mechanisms behind seizures. “… we focused on the LPI-GPR55 signaling pathway as a potential modulator of E:I ratio and anti-seizure target of CBD.

To do this they used a variety of techniques that included measuring information-carrying electrical current flows with fine-tipped electrodes, or by investigating the effect of LPI by genetically removing its main signaling partner, or by measuring the release of LPI following seizures. Their collective results confirmed past findings that LPI influences nerve signals by binding to GPR55, on neuron cell surfaces. This LPI-GPR55 presynaptic interaction was found to cause the release of calcium ions within the cell, which encouraged cells to release glutamate, the main excitatory neurotransmitter.

Further, when LPI activated GPR55 on the other side of the synapse, it weakened inhibition, by decreasing the supply and proper arrangement of proteins necessary for inhibition. Collectively, this creates a “dangerous” two-pronged mechanism to increase excitability, say the authors. “We found that LPI triggers aGPR55-dependent dual mechanism to elevate network excitability: a transient elevation in presynaptic excitatory release probability, complemented by a slower sustained reduction of inhibitory synaptic strength,” the investigators stated.

The research team found that LPI-mediated effects on both excitatory and inhibitory synaptic transmission could be blocked either by genetically engineering mice to lack GPR55, or by treating mice with plant-derived CBD prior to seizure-inducing stimuli. While prior studies had implicated GPR55 as a seizure-reducing target of CBD, the current work provided a more detailed, proposed mechanism of action.

The authors propose that CBD blocks a positive feedback loop in which seizures increase LPI-GPR55 signaling, which likely encourages more seizures, which in turn increases levels of both LPI and GPR55. “Our observations suggest a positive feedback loop whereby LPI promotes hyperexcitability, which in turn increases the expression of LPI and GPR55,” they further explained. “We tentatively propose that CBD can extinguish a potentially regenerative loop in which hyperactivity enhances LPI-GPR55 signaling, further shifting the E:I ratio … Our experiments provide new insights on synaptic mechanisms of CBD’s anti-seizure effects.”

The team concluded that CBD could represent a potential therapeutic agent in treatment-resistant epilepsy patients who don’t respond to current drugs, such as benzodiazepines, possibly due to LPI-GPR55 effects.

The proposed vicious cycle also represents one process that could explain repeated epileptic seizures, although future studies are needed to confirm this. Further, the current study examined the plant-based cannabinoid CBD, but the authors note that LPI is part of signaling network that includes endocannabinoids such as 2-Arachidonoylglycerol (2-AG) that occur naturally in human tissues. LPI and 2-AG target receptors also regulated by CBD, but have different actions at the synapse. While LPI amplifies incoming electrical signals, endocannabinoids such as 2-AG respond to increases in brain activity by dialing down the release of neurotransmitters from nerve cells. Interestingly, LPI and 2-AG can be converted into each other through actions of enzymes.

“Theoretically, the brain could control activity by toggling between pro-excitatory LPI and the restorative actions of 2-AG,” said first study author Evan Rosenberg, PhD, a postdoctoral scholar in the Tsein’s lab. “Drug designers could inhibit the enzymes that underpin LPI production or promote its conversion to 2-AG, as an additional approach to control seizures. LPI could also serve as a biomarker of seizures or predictor of clinical responsiveness to CBD, providing an area of future research.”

Tue, 14 Feb 2023 23:00:00 -0600 en-US text/html https://www.genengnews.com/marijuana/cannabinoids/cbd-counters-hippocampal-hyperactivity-in-epilepsy/
Killexams : Study reveals how CBD counters epileptic seizures

A study reveals a previously unknown way in which cannabidiol (CBD), a substance found in cannabis, reduces seizures in many treatment-resistant forms of pediatric epilepsy.

Led by researchers at NYU Grossman School of Medicine, the new study found that CBD blocked signals carried by a molecule called lysophosphatidylinositol (LPI). Found in called neurons, LPI is thought to amplify as part of normal function, but can be hijacked by disease to promote seizures.

Published online February 13 in Neuron, the work confirmed a previous finding that CBD blocks the ability of LPI to amplify nerve signals in a brain region called the hippocampus. The current findings argue for the first time that LPI also weakens signals that counter seizures, further explaining the value of CBD treatment.

"Our results deepen the field's understanding of a central seizure-inducing mechanism, with many implications for the pursuit of new treatment approaches," said corresponding author Richard W. Tsien, chair of the Department of Physiology and Neuroscience at NYU Langone Health.

"The study also clarified, not just how CBD counters seizures, but more broadly how circuits are balanced in the brain," added Tsien. "Related imbalances are present in autism and schizophrenia, so the paper may have a broader impact."

The study results build on how each neuron "fires" to send an electrical pulse down an extension of itself until it reaches a synapse, the gap that connects it to the next cell in a neuronal pathway. When it reaches the cell's end before the synapse, the pulse triggers the release of compounds called neurotransmitters that float across the gap to affect the next cell in line. Upon crossing, such signals either encourage the cell to fire (excitation), or apply the brakes on firing (inhibition). Balance between the two are essential to brain function; too much excitation promotes seizures.

The new study looked at several rodent models to explore mechanisms behind seizures, often by measuring information-carrying electrical current flows with fine-tipped electrodes. Other experiments looked at the effect of LPI by genetically removing its main signaling partner, or by measuring the release of LPI following seizures.

The tests confirmed past findings that LPI influences nerve signals by binding to a protein called G-coupled receptor 55 (GPR55), on neuron cell surfaces. This LPI-GPR55 presynaptic interaction was found to cause the release of calcium ions within the cell, which encouraged cells to release glutamate, the main excitatory neurotransmitter. Further, when LPI activated GPR55 on the other side of the synapse, it weakened inhibition, by decreasing the supply and proper arrangement of proteins necessary for inhibition. Collectively, this creates a "dangerous" two-pronged mechanism to increase excitability, say the authors.

The research team found that either genetically engineering mice to lack GPR55, or treating mice with plant-derived CBD prior to seizure-inducing stimuli, blocked LPI-mediated effects on both excitatory and inhibitory synaptic transmission. While prior studies had implicated GPR55 as a -reducing target of CBD, the current work provided a more detailed, proposed mechanism of action.

The authors propose that CBD blocks a "positive feedback loop" in which seizures increase LPI-GPR55 signaling, which likely encourages more seizures, which in turn increases levels of both LPI and GPR55. The proposed vicious cycle provides one process that could explain repeated , although future studies are needed to confirm this.

Further, the current study examined the plant-based cannabinoid CBD, but the authors note that LPI is part of signaling network that includes "endocannabinoids" like 2-Arachidonoylglycerol (2-AG) that occur naturally in human tissues. LPI and 2-AG target receptors also regulated by CBD, but have different actions at the synapse. While LPI amplifies incoming electrical signals, endocannabinoids like 2-AG respond to increases in by dialing down the release of neurotransmitters from nerve cells. Interestingly, LPI and 2-AG can be converted into each other through actions of enzymes.

"Theoretically, the brain could control activity by toggling between pro-excitatory LPI and the restorative actions of 2-AG," said first study author Evan Rosenberg, Ph.D., a post-doctoral scholar in the Tsein's lab. "Drug designers could inhibit the enzymes that underpin LPI production or promote its conversion to 2-AG, as an additional approach to control seizures. LPI could also serve as a biomarker of or predictor of clinical responsiveness to CBD, providing an area of future research."

More information: Richard Tsien & colleauges, Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity, Neuron (2023). DOI: 10.1016/j.neuron.2023.01.018. www.cell.com/neuron/fulltext/S0896-6273(23)00066-1

Citation: Study reveals how CBD counters epileptic seizures (2023, February 13) retrieved 19 February 2023 from https://medicalxpress.com/news/2023-02-reveals-cbd-counters-epileptic-seizures.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.

Sun, 12 Feb 2023 10:01:00 -0600 en text/html https://medicalxpress.com/news/2023-02-reveals-cbd-counters-epileptic-seizures.html
Killexams : Study elucidates how cannabidiol reduces seizures in treatment-resistant pediatric epilepsy

A study reveals a previously unknown way in which cannabidiol (CBD), a substance found in cannabis, reduces seizures in many treatment-resistant forms of pediatric epilepsy.  

Led by researchers at NYU Grossman School of Medicine, the new study found that CBD blocked signals carried by a molecule called lysophosphatidylinositol (LPI). Found in brain cells called neurons, LPI is thought to amplify nerve signals as part of normal function, but can be hijacked by disease to promote seizures.

Published online February 13 in Neuron, the work confirmed a previous finding that CBD blocks the ability of LPI to amplify nerve signals in a brain region called the hippocampus. The current findings argue for the first time that LPI also weakens signals that counter seizures, further explaining the value of CBD treatment.  

Our results deepen the field's understanding of a central seizure-inducing mechanism, with many implications for the pursuit of new treatment approaches."

Richard W. Tsien, PhD, corresponding author, chair of the Department of Physiology and Neuroscience at NYU Langone Health

"The study also clarified, not just how CBD counters seizures, but more broadly how circuits are balanced in the brain," adds Dr. Tsien, also director of NYU Langone's Neuroscience Institute. "Related imbalances are present in autism and schizophrenia, so the paper may have a broader impact."

The study results build on how each neuron "fires" to send an electrical pulse down an extension of itself until it reaches a synapse, the gap that connects it to the next cell in a neuronal pathway. When it reaches the cell's end before the synapse, the pulse triggers the release of compounds called neurotransmitters that float across the gap to affect the next cell in line. Upon crossing, such signals either encourage the cell to fire (excitation), or apply the brakes on firing (inhibition). Balance between the two is essential to brain function; too much excitation promotes seizures.  

The new study looked at several rodent models to explore mechanisms behind seizures, often by measuring information-carrying electrical current flows with fine-tipped electrodes. Other experiments looked at the effect of LPI by genetically removing its main signaling partner, or by measuring the release of LPI following seizures.

The tests confirmed past findings that LPI influences nerve signals by binding to a protein called G-coupled receptor 55 (GPR55) on neuron cell surfaces. This LPI-GPR55 presynaptic interaction was found to cause the release of calcium ions within the cell, which encouraged cells to release glutamate, the main excitatory neurotransmitter.

Further, when LPI activated GPR55 on the other side of the synapse, it weakened inhibition, by decreasing the supply and proper arrangement of proteins necessary for inhibition. Collectively, this creates a "dangerous" two-pronged mechanism to increase excitability, say the authors.  

The research team found that either genetically engineering mice to lack GPR55, or treating mice with plant-derived CBD before seizure-inducing stimuli, blocked LPI-mediated effects on both excitatory and inhibitory synaptic transmission. While prior studies had implicated GPR55 as a seizure-reducing target of CBD, the current work provided a more detailed, proposed mechanism of action.

The authors propose that CBD blocks a "positive feedback loop" in which seizures increase LPI-GPR55 signaling, which likely encourages more seizures, which in turn increases levels of both LPI and GPR55. The proposed vicious cycle provides one process that could explain repeated epileptic seizures, although future studies are needed to confirm this.

Further, the current study examined the plant-based cannabinoid CBD, but the authors note that LPI is part of signaling network that includes "endocannabinoids" like 2-Arachidonoylglycerol (2-AG) that occur naturally in human tissues. LPI and 2-AG target receptors also regulated by CBD, but have different actions at the synapse. While LPI amplifies incoming electrical signals, endocannabinoids like 2-AG respond to increases in brain activity by dialing down the release of neurotransmitters from nerve cells. Interestingly, LPI and 2-AG can be converted into each other through actions of enzymes.

"Theoretically, the brain could control activity by toggling between pro-excitatory LPI and the restorative actions of 2-AG," says first study author Evan Rosenberg, PhD, a postdoctoral scholar in the Tsien lab. "Drug designers could inhibit the enzymes that underpin LPI production or promote its conversion to 2-AG, as an additional approach to control seizures. LPI could also serve as a biomarker of seizures or predictor of clinical responsiveness to CBD, providing an area of future research."

Along with Dr. Tsien and Dr. Rosenberg, study authors in the Department of Neuroscience and Physiology and Neuroscience Institute at NYU Langone were Simon Chamberland, Erica Nebet, Xiaohan Wang, Sam McKenzie, Alejandro Salah, Nicolas Chenouard, Simon Sun, and György Buzsáki, MD, PhD. NYU Langone authors also were Orrin Devinsky, MD, in the Department of Neurology, Rebecca Rose in the Division of Advanced Research Technologies, and Drew R. Jones, PhD, in the Department of Biochemistry and Molecular Pharmacology.

Source:

Journal reference:

Rosenberg, E.C., et al. (2023) Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity. Neuron. doi.org/10.1016/j.neuron.2023.01.018.

Sun, 12 Feb 2023 10:01:00 -0600 en text/html https://www.news-medical.net/news/20230213/Study-elucidates-how-cannabidiol-reduces-seizures-in-treatment-resistant-pediatric-epilepsy.aspx
Killexams : Managing Risk in Aseptic Processing Environments

By Jeong Jin-hyeok

Jeong Jin-hyeok
Jeong Jin-hyeok

To assure patient safety, biologics developers and manufacturers must carefully consider where contaminants could be introduced to the drug substances (DSs) or drug products (DPs) at all stages of the drug lifecycle. From the filling lines, containers, and stoppers to the air in the surrounding manufacturing space, biologics producers must understand the sources of risk, create a highly controlled environment, and constantly monitor for potential breaches.

In this article, I will outline strategies developers should employ to protect biologic DSs and DPs. I will also explore key monitoring tactics to help maintain a sterile environment.

A sanitary manufacturing process for producing therapeutics is crucial to ensure the safety of patients receiving all forms of treatment—especially those seen with biologics. Most biologics will be administered via injection, enabling delivery directly to the bloodstream.

As parenteral drugs bypass many of the body’s natural defenses, a greater risk of infection may arise if these products are not sterile as compared with other dosage forms. To protect patients from serious infectious diseases, such as meningitis and sepsis, sterility must be of utmost importance.1

Developers and manufacturers of parenteral therapeutics also aim to attain sterility to ensure compliance. Regulatory bodies, including the FDA and the EMA, have published stringent guidance documents and recommendations for the aseptic processing of sterile DPs.2,3

Failure to prevent contamination of parenteral biologic products could bring a number of consequences, including delays, safety risks, recalls, remediation costs, and denied approvals. The risks associated with sterility breaches and the potential financial costs involved in their rectification mean it is critical to implement robust strategies for preserving aseptic conditions.

Through careful sterility checks and controls, aseptic processing maintains sterile conditions during manufacturing and protects against breaches. Aseptic processing necessitates extensive training and experience from operators and handlers. From formulation to filling, and from inspection to labeling and packaging, developers must also adhere to current Good Manufacturing Process (cGMP) standards and consider how sterility assurance can be monitored at different points of the aseptic process.

Meeting sterility demands requires facilities capable of constantly monitoring for contamination breaches. Therefore, biologic drug developers need to implement a robust approach to maintain an aseptic process, which should include the following monitoring and testing steps.

Detecting prior contamination

An important initial step when receiving a DS from another facility is to ensure that the material is not already contaminated. In vitro assays can be used to assess DS viral contamination, and similar analyses can be carried out to detect the presence of mycoplasma.

As a common bacterial contaminant with resistance to many antibiotics, mycoplasma poses a high risk to patients. Accordingly, determining the presence of mycoplasma is critical. However, mycoplasmas are often difficult to detect without chemical tests, as mycoplasmas are apt to be smaller than other common bacterial contaminants.

Bioburden reduction filtration

For many pharmaceutical products, terminal sterilization processes, such as steam or irradiation, ensure the product is sterile in its final container. As these harsh conditions can damage the efficacy of the biologic, many biopharma developers will instead need to rely on sterile filtration and subsequent aseptic processes.

After the DS is formulated but before fill-finish, DS containers will either be thawed or brought to equilibrium for bioburden reduction filtration. The DS will be mixed and pumped into a filling unit with a validated flow rate, where a series of two 0.22-µm filters will ensure that bacterial or any other cellular matter is absent from the final formulation. After sterile filtration, the product should be filled in an aseptic environment into the final container and sealed, at which point the material is considered a DP.

Meeting the Master Specification

The final steps should follow the Master Specification, which outlines the requirements for meeting quality and performance outcomes in finished products. Besides conducting a visual inspection, developers should perform Container Closure Integrity Testing (CCIT) to assess the fitting of stoppers and vials during the fill-finish stage. CCIT will determine whether a true seal has been made between the vial and stopper, preventing contamination from microbial organisms. A selection of vials should be used for quality control testing following the DP specification to ensure that vials are suitable for distribution and patient use.

Environmental controls

In addition to the necessary sterilization steps, a number of environmental controls can be utilized to further limit contamination risk. Environmental controls will assess the air quality and pressure, temperature, ventilation, and humidity, in addition to detecting the presence of external microbes. Well-established environmental controls are a must to comply with cGMP requirements.

One example of environmental control is the implementation of a Restricted Access Barrier System (RABS), which protects process materials from potential contaminants in the environment through a barrier and positive airflow. Air quality within the RABS filling unit can be monitored using both viable and nonviable particulate counters. Utilizing both counters enables real-time monitoring and reduces the need for aseptic interventions, making it easier to establish a cause of contamination if a breach were to occur.

Another appropriate environmental control is the use of contact plates within the RABS filling unit to detect the presence of bacteria. Personnel working within the filling room should be monitored by using contact plates.

Single-use systems within aseptic processing

Another way to reduce cross-contamination risk during DP production is through the use of single-use systems, including components like formulation bags and filling tubing pathways, which should be assessed as a part of the cross-contamination strategy.

When using equipment that is not single use, it is important to certain the effective cleaning of equipment. Remnants of previous products should not be left behind on contact surfaces. Validation of cleaning systems and the use of stainless steel or another easy-to-clean equivalent material within the filling systems will be needed to ensure cleaning protocols are consistently effective.

The burden of cleaning validation requirements means there is a trending preference in the industry toward using single-use systems to avoid the additional labor, higher costs, and longer timelines generally associated with reusable equipment.

The importance of expertise and experience in aseptic processing

As aseptic processes and systems may require adaptation depending on the unique needs of processes or molecules manufactured, there is a critical need for experience and expertise. When working with a contract development and manufacturing organization (CDMO), it is important to work in partnership to perform a complete technical analysis and a robust technology transfer process. Developers will also need to evaluate equipment and processes based on the critical process parameters (CPPs) and critical quality attributes (CQAs) of each product. The approach to selecting sterilization methods will be project specific and tailored to each molecule.

The comprehensive training for personnel and specialized facilities needed for aseptic processing mean that it is advantageous to seek support from CDMOs, rather than spending time and money expanding in-house capabilities. The benefits of using a CDMO are vast, including gaining the expertise and experience of seasoned scientists and immediate access to purpose-built facilities.

Key lessons

Contaminant breaches in biologics manufacturing are associated with many risks, from negative impacts on patient health to financial losses and reputational setbacks. Preventing contaminant risk means great care must be taken to ensure that the final product is sterile through the implementation of various checks, controls, and measures. With so many factors that must be considered throughout aseptic processing, biopharma developers can alleviate the burden by relying on CDMO partners with the necessary experience and expertise to minimize risk.

References
1. Virtanen S, Kapp K, Rautamo M, et al. Compounding Parenteral Products in Pediatric Wards-Effect of Environment and Aseptic Technique on Product Sterility. Healthcare (Basel) 2021; 9(8): 1025. DOI: 10.3390/healthcare9081025.
2. U.S. Food and Drug Administration. Guidance for Industry on Sterile Drug Products Produced by Aseptic Processing—Current Good Manufacturing Practice (September 2004). Updated May 4, 2020. Accessed January 10, 2023.
3. European Medicines Agency. Guideline on the sterilisation of the medicinal product, active substance, excipient and primary container (March 6, 2019). Accessed January 10, 2023.

Jeong Jin-hyeok is lead engineer, drug products at Samsung Biologics.

 

Wed, 01 Feb 2023 16:58:00 -0600 en-US text/html https://www.genengnews.com/topics/bioprocessing/managing-risk-in-aseptic-processing-environments/
Killexams : Is ITOM Still Relevant for Multi-cloud Environments?

IT Operations management (ITOM) – a framework that gives IT teams the tools to centrally monitor and manage applications and infrastructure across multi-premise environments – has been the foundation of enterprise IT infrastructure and applications for the last 30 years. It has been the backbone that ensures technology stacks are operating optimally to provide timely business value and keep employees engaged and productive by maintaining the availability of core applications. But the accurate acceleration of digital transformation across global industries and emergence of multi-cloud environments has introduced a new level of complexity.

While flexibility, elasticity, and ease of use are benefits that make starting with the cloud an enticing prospect, ongoing operation and management can quickly become difficult to oversee. As the business scales across infrastructure and applications deployments in a multi-cloud environment, so does the complexity inherent in diverse cloud operating models and tools, and distributed application architecture and deployment. Many IT professionals also lack technical or management skills in these areas.

According to a recent VMware survey of tech executives and their priorities for digital momentum, 73% reported a push to standardize multi-cloud architectures. The digital transformation and transition to multi-cloud environments to bring the best technology stacks that unlock business value will be a journey for most global enterprises in the coming years. The key is how to empower cloud-focused or cloud-native technology teams to realize the full potential of their transformational investments in multi-cloud environments.

This prompts a key question: is ITOM still valid when it comes to managing enterprise technology stacks that are increasingly categorized as multi-cloud environments?

IT operators for years had their favorite tools to manage infrastructure, applications, databases, networks, and more to support the needs of their business. But with the growing workload migration to multi-cloud environments, IT pros are now scrambling between siloed operations tools and cloud-specific tools provided by the key hyperscalers – AWS, Azure, or Google – for specific use cases. This tool sprawl is often exacerbated by the enterprises’ desire to pick the best cloud platform based on the problem that needs to be resolved. For a .NET based application migration to the cloud, for example, Azure might be the better choice, while an AI/ML large data lake analysis could be best suited to run on Google Cloud.

This is where ITOM is evolving to bring a holistic and comprehensive view across multiple disciplines of multi-cloud infrastructure and applications, integrating best practices from cost, operations, and automation management principles along with connected data. ITOM has been leveraged for decades in enterprise on-premises environments to bring disparate, federated, and integrated tools together to operate in a secure way. The key to success in accelerating digital transformation in multi-cloud consumption era is to have complete visibility of the environment, automation of mundane tasks, and proactive operations that utilize connected data from multiple domains in near real-time to drive preventive and proactive insights. This is possible to achieve with an integrated platform that brings different domains of operations, costs, and automation on a single integrated data platform.

There are different ITOM incumbents trying to “cloudify” their current solutions by tucking AIOps into the mix and integrating with application performance management (APM) offerings. On the other hand, there are also new market disrupters joining the race to provide a single integrated solution for the enterprises that unify multiple domains and data together to provide visibility, operations, cost, optimization, and automation across multi-cloud environments. All these scenarios suggest ITOM will solidify itself as even more relevant in cloud and modern IT operations management now and in the future – but to maximize its value, IT teams must move from cloud chaos to cloud smart management.

There are three primary characteristics of a cloud-smart IT operations management solution enterprises should look for:

  1. Platform and API-based Solutions: Look for solutions that bring a set of common and integrated services together to monitor, observe, manage, optimize, and automate across infrastructure and apps. By using solutions that take a platform and API-first approach, IT teams are empowered to technology-proof their investments from a state of continuous invention and reinvention of the enterprise’s technology stacks and solutions. These types of offerings also help teams to connect the old legacy technology with more modern solutions as they progress along their digital transformation journeys while maintaining and growing their business.
  2. Integrated Data-driven Operations: A good ITOM solution should provide data-driven intelligence across multiple data domains to inform proactive decisions that leverage AIOps 2.0 principles. – AIOps must take a data-driven automation-first and self-service approach to truly provide value that frees resources to drive value-based development and delivery instead of chasing reactive problems. Global digital businesses are operating in multi-cloud environments, at the edge, and everywhere in between alongside the people, processes, and things that provide contextual customer experience. CloudOps will further provide rich diverse data to turn contextual connected data into business insights. It can’t manage an old school events-based command center but instead provides context across distributed and connected layers of technology by processing diverse volumes and variety of data that can be observed through business KPIs to drive actions to resolution. This will enable the modern digital businesses to constantly optimize the network and make informed decisions eliminating mundane manual tasks to Boost productivity and innovation.
  3. Continuous Consumptions, Agility, and Control: We are moving from a static on-premises environment to dynamic cloud environments in the digital business, leveraging ephemeral workflows. This is where the right tools will drive automation of repetitive mundane tasks, enable governance and controls on cost, usage, and policy for the ever-changing business needs that demand elastic resources, data driven process accommodation, dynamic configurations, and consumption pricing.

The world of multi-cloud, edge, and on-premises are here to stay to drive the digital transformation journey of the enterprise. However, the pendulum of workloads moving between those discrete environments will continue to shift as business, compliance, and governance requirements change. ITOM and ITOps approaches are more relevant than ever in the world of multi-cloud hybrid environments with distributed ephemeral workloads (as they once were on on-premises environments). Still, it’s imperative that these operations management frameworks evolve with changing needs of business to ensure they’re able to simplify complex distributed technology stacks and cumbersome manual processes.

The goal is to drive contextual observable insights that lead to optimized usage and consumptions-based cultures by connecting different functions of business users, technology developers, and operators while enhancing complete end-to-end visibility of technology architectures. Only then can an organization benefit from modern ITOM that enables continuous change, compliance, and optimization to support a vibrant global business and its customers.

To learn more, visit us here.

Tue, 31 Jan 2023 02:32:00 -0600 en-US text/html https://www.cio.com/article/420394/is-itom-still-relevant-for-multi-cloud-environments.html
Killexams : This Might Be The World’s Most Striking Lamborghini Countach LPI 800-4

This Lamborghini Countach LPI 800-4 sits on a bespoke set of Anrky wheels

January 30, 2023 at 13:47

by Brad Anderson

While many remain unconvinced by Lamborghini’s decision to revive the famed Countach nameplate with an Aventador-based model, there’s no denying that this particular example is a real head-turner.

This Countach LPI 800-4 resides in Japan and is quite possibly the most outlandish anywhere on earth. This is thanks to Lamborghini itself, as well as Anrky Wheels.

Read: Lamborghini Delivered The First Two U.S. Countach LPI 800-4s At Monterey

For starters, the exterior of this Countach LPI 800-4 is bathed in a Chameleon-inspired paint scheme that changes color depending on the angle at which it is viewed. The main colors you’ll notice are orange, red, pink, purple, blue, and an eye-catching shade of bronze. Then there are the wheels.

Dubbed the X|Series S3-X0, these wheels have a gold-painted finish and suit the design of the modern-day Countach absolutely perfectly. They sit over a set of red brake calipers.

advertisement scroll to continue

Lamborghini is building just 112 examples of the Countach LPI 800-4 and ever since deliveries commenced in mid-2022, we’ve seen a host of particularly eye-catching examples handed over to their owners. One of the more intriguing was delivered in Canada back in October and is painted in Verde Abete, a British Racing Green that’s been contrasted with a set of bronze wheels.

As you may know already, the Countach LPI 800-4 has the same hybrid powertrain as the limited-run Sian FKP 37. This means it is rocking a 6.5-liter naturally-aspirated V12 supplemented by a 48-volt hybrid system and an electric motor to deliver a total of 803 hp and 531 lb-ft (735 Nm) of torque. The car can hit 60 mph (96 km/h) in just 2.8 seconds and won’t stop accelerating until it hits 221 mph (355 km/h).

 This Might Be The World’s Most Striking Lamborghini Countach LPI 800-4
Ankywheels/Lager_Corp
Mon, 30 Jan 2023 06:27:00 -0600 en text/html https://www.carscoops.com/2023/01/this-might-be-the-worlds-most-striking-lamborghini-countach-lpi-800-4/
Killexams : Lamborghini Countach In Blu Hal Is The Only Modified LPI 800-4 In The World

Lowered suspension and wheels are all you need when you spec a stunning paint job like this.

The Lamborghini Countach LPI 800-4 was revealed in 2021 as a special edition of which only 112 examples would be made, but that hasn't stopped one wealthy buyer from putting his own spin on the car by lowering it.

As such a rare and special creation, it's no surprise that this is the only modified Countach in the world, but you may be surprised to learn that the spectacular finish on the body is not part of the aftermarket changes. This is a factory-applied paint finish called Blu Hal, and it's reminiscent of the iridescent, pearlescent hues you'd find on TVR Tuscans finished in ChromaFlair. JDM fans will recall the similarities to Midnight Purple, as seen on various Nissan Skyline GT-R models.

Since so few Countach special editions were to be produced, this is probably also the only one in the world in this color. But let's talk about the modifications.

This particular car lives in Japan and has been lightly tuned with easily reversible modifications, so if you're a purist, hold your horses.

The two-piece wheels are some of the latest from ANRKY Wheels' X Series, called S2-X0. They're presented in an attention-grabbing Mirror Polished Gold finish. Behind these, you can see red calipers, which match the upholstery in the cabin.

The only other modification is a static (not air suspension) lowering kit. As long as the owner doesn't scrape the underbelly or the lip (and avoids any irreversible modifications), these changes should not negatively impact the future value of the car.

Mon, 30 Jan 2023 22:46:00 -0600 en-us text/html https://carbuzz.com/news/lamborghini-countach-in-blu-hal-is-the-only-modified-lpi-800-4-in-the-world
300-100 exam dump and training guide direct download
Training Exams List