CNS Pharmacology

Mental disorders tend to co-exist together and anxiety is likely to co-morbid with depression. The aim of this study is to discover a safe and natural herbal source of remedy with minimum side effects in the form of Tamarindus indica. As rodents are neuro-anatomically and neuro-pharmacologically parallel to human, so Tamarindus indica was administered orally in 3 different doses of 50mg/kg, 75mg/kg and 100mg/kg to 3 different groups of mice having equal sex distribution and  n=7 for 21 days. The CNS acting potential evaluated by behavioral responses, head dip method, cage crossings and force induced swimming test. The results revealed that Tamarindus indica is a potent anxiolytic agent even at low dose of 50mg/kg without sedative effects but showing low mood and week muscle tone whereas dose dependent antidepressant activity was also seen which is prominent at the high dose of 100mg/kg showing CNS alertness, elevation of mood, increase in learning behavior and overall improved performance of mice.

Objective of the study was to find out the Resistogram of the urinary isolates against different commonly prescribed antimicrobials according to CLSI guidelines. Out of total 319 test samples, in 56 cases bacterial pathogens were isolated. Among those 56 isolates only 13 were resistant to Nitrofurantoin (23.21%) where as resistance to Ciprofloxacin was found in 40 isolates(71.42%), resistance against Co-Trimoxazole was found in 27 isolates (48.21%) and surprisingly, resistance against Carbapenem antibiotics (Meropenem) was in 20 isolates (35.71%). Majority of the Nitrofurantoin resistant bacterial isolates were Klebsiella pneumoniae (4 out of 13 i.e, 30.76%). All Nitrofurantoin resistant isolates were sensitive to both Tigecycline and Colistin and the isolated Escherichia coli (two in number) were sensitive to Meropenem also. There were no other therapeutic options like Fluroquinolones or Co-trimoxazole to manage the Nitrofurantoin resistant isolates as all of them were resistant to...

Objective structured practical examination (OSPE) a new
assessment tool has been implemented in a few medical colleges.
This method of assessment was planned to be implemented in our
medical college, before which the authors planned to compare the
scores obtained by the students by conventional method of
examination and OSPE. The marks obtained by the two methods
of examination were compared and a feedback was collected from
students to study their perspective towards OSPE. There was
statistically significant difference in the mean of the scores
obtained by conventional method and that of OSPE. The students’
perception about OSPE was good. This study enabled the authors
to standardize the pattern of OSPE and implement it.

The blood-brain barrier (BBB) poses a unique challenge for drug delivery to the central nervous system (CNS). The BBB consists of a continuous layer of specialized endothelial cells linked together by tight junctions, pericytes, nonfenestrated basal lamina, and astrocytic foot processes. This complex barrier controls and limits the systemic delivery of therapeutics to the CNS. Several innovative strategies have been explored to enhance the transport of therapeutics across the BBB, each with individual advantages and disadvantages. Ongoing advances in delivery approaches that overcome the BBB are enabling more effective therapies for CNS diseases. In this review, we discuss: (1) the physiological properties of the BBB, (2) conventional strategies to enhance paracellular and transcellular transport through the BBB, (3) emerging concepts to overcome the BBB, and (4) alternative CNS drug delivery strategies that bypass the BBB entirely. Based on these exciting advances, we anticipate that in the near future, drug delivery research efforts will lead to more effective therapeutic interventions for diseases of the CNS.

Use of the members of the genus Allium L. in Northeast India is quite
significant  from  the  perspective  of  ethnopharmacology.  The
pharmacological aspect of the genus Allium L. have been clinically
evaluated  since  long  due  to  its  typical  flavour  and  ethnomedicinal
importance. The plants posses a number of chemical constituents like
sulphur,  allicin  etc.  that  are  responsible  for  certain  biological
activities  of  pharmacological  importance  including  anticancer
activity.  Several  species  of  Allium  L.    have  been  reported  from
northeast  India  having  ethnobotanical  uses  and  are  very  popular
among  the  ethnic  groups  either  as  spice/vegetables  or  in  folk
medicine. Considering the importance of the plants in this region a
thorough  review  of  literature  was  undertaken  to  prepare  a
consolidated account of ethnobotany and pharmacological activities
of the species occurring in northeast India

implications for global health. It is the fourth leading cause of
death in the United States, exceeded only by heart attacks, cancers,
and stroke. This can result from several types of anatomical
lesions, including loss of lung elastic recoil and fibrosis and
narrowing of small airways. Inflammation, edema, and secretions
also contribute variably to airflow limitation. Occupational
exposure to dusts and chemicals, asthma, age, tobacco smoke and
genetic factors likely play a major role and which also account for
much of the heterogeneity susceptibility to smoke and other
factors. Many factors may play a role, but to date, only α-1
protease inhibitor deficiency has been unambiguously identified.
Exposures other than cigarette smoke can also contribute to the
development of COPD. Spirometry is recommended in COPD
guidelines for the accurate diagnosis of this disease. Wheezing,
productive cough, barrel chest and shortness of breath are some of
the hallmark signs of COPD. Although COPD cannot be cured
but it can be managed my reducing symptoms and improving
overall health, WHO and NICE have guidelines regarding COPD
which outline management via pharmacotherapy for approaching
COPD. The advances in understanding the pathogenesis of COPD
have identified the provided therapy for management of this
disease, if these guidelines are accurately followed, reduction in
further complications or mortality from this ailment can be
achieved.

Objective of the study was to find out the Resistogram of the urinary
isolates  against  different  commonly  prescribed  antimicrobials
according  to  CLSI  guidelines.  Out  of  total  319  test samples,  in  56
cases  bacterial  pathogens  were  isolated.  Among  those  56  isolates
only 13 were resistant to Nitrofurantoin (23.21%) where as resistance
to Ciprofloxacin was found in 40 isolates(71.42%), resistance against
Co-Trimoxazole was found in 27 isolates (48.21%) and surprisingly,
resistance  against  Carbapenem  antibiotics  (Meropenem)  was  in  20
isolates  (35.71%).  Majority  of  the  Nitrofurantoin  resistant  bacterial
isolates  were  Klebsiella  pneumoniae (4  out  of  13  i.e,  30.76%).  All
Nitrofurantoin  resistant  isolates  were  sensitive  to  both  Tigecycline
and Colistin and the isolated  Escherichia coli(two in number) were
sensitive to Meropenem also. There were no other therapeutic options
like Fluroquinolones or Co-trimoxazole to manage the Nitrofurantoin
resistant isolates as all of them were resistant tothem. Thus medical
community  should  think  twice  before  replacing  Nitrofurantoin  with
Fluroquinolones or Co-Trimoxazoles as emperical therapy.

Aim: To determine the prescribing rate and pattern of antiparkinson drug use and to assess associated adverse drug reactions in patients with idiopathic Parkinson disease.
Materials and methods: Data was collected from the outpatients in neurology and medical records department. Patient demography, disease duration, symptoms, comorbid conditions, drug, dose, adverse drug reaction if any were noted. Information was collected again from the study participants during their routine follow up visit three months later to monitor the symptoms and adverse drug reactions (if any) occurring due to treatment. Causality assessment was done for the ADRs reported based on WHO scale.
Results: Male predominance was seen. A majority of patients were between 51 and 80 years and most of the patients had onset of disease between 51 and 70 years. The common presenting symptoms were rigidity, tremor and bradykinesia. Out of 100 patients, 48 received levodopa+carbidopa alone and the rest received combination therapy. The number of antiparkinson drug prescriptions increased with the disease duration. Sixty three patients had subjective improvement in the symptoms, of which bradykinesia was most common. Levodopa induced dyskinesia was the most common adverse drug reaction. The number of adverse drug reactions was significantly higher among patients receiving combination therapy.
Conclusion: Our study provides a basic knowledge about the drug prescribing pattern in the treatment of Parkinson disease and also the adverse reactions to the drugs prescribed.

Peptidylarginine deiminases are a family of calcium-activated enzymes with multifaceted roles in physiological and pathological processes, including in the central nervous system. Peptidylarginine deiminases cause post-translational deimination/citrullination, leading to changes in structure and function of a wide range of target proteins. Deimination can facilitate protein moonlighting, modify protein-protein interaction, cause protein dysfunction and induce inflammatory responses. Peptidylarginine deiminases also regulate the biogenesis of extracellular vesicles, which play important roles in cellular communication through transfer of extracellular vesicle-cargo, e.g., proteins and genetic material. Both peptidylarginine deiminases and extracellular vesicles are linked to a number of pathologies, including in the central nervous system, and their modulation with pharmacological peptidylarginine deiminase inhibitors have shown great promise in several in vitro and in vivo central nervous system disease models. Furthermore, extracellular vesicles derived from mesenchymal stem cells have been assessed for their therapeutic application in central nervous system injury. As circulating extracellular vesicles can be used as non-invasive liquid biopsies, their specific cargo-signatures (including deiminated proteins and microRNAs) may allow for disease "fingerprinting" and aid early central nervous system disease diagnosis, inform disease progression and response to therapy. This mini-review discusses recent advances in the field of peptidylarginine deiminase and extracellular vesicle research in the central nervous system, focusing on several central nervous system acute injury, degeneration and cancer models.

These authors have contributed equally to this work Specialty section: This article was submitted to Embryonic and Developmental Physiology, a section of the journal Frontiers in Physiology Hypoxic-ischemic encephalopathy (HIE) is a major cause of mortality and morbidity in neonates, with an estimated global incidence of 3/1,000 live births. HIE brain damage is associated with an inflammatory response and oxidative stress, resulting in the activation of cell death pathways. At present, therapeutic hypothermia is the only clinically approved treatment available for HIE. This approach, however, is only partially effective. Therefore, there is an unmet clinical need for the development of novel therapeutic interventions for the treatment of HIE. Curcumin is an antioxidant reactive oxygen species scavenger, with reported anti-tumor and anti-inflammatory activity. Curcumin has been shown to attenuate mitochondrial dysfunction, stabilize the cell membrane, stimulate proliferation, and reduce injury severity in adult models of spinal cord injury, cancer, and cardiovascular disease. The role of curcumin in neonatal HIE has not been widely studied due to its low bioavailability and limited aqueous solubility. The aim of this study was to investigate the effect of curcumin treatment in neonatal HIE, including time of administration and dose-dependent effects. Our results indicate that curcumin administration prior to HIE in neonatal mice elevated cell and tissue loss, as well as glial activation compared to HI alone. However, immediate post-treatment with curcumin was significantly neuroprotective, reducing grey and white matter tissue loss, TUNEL+ cell death, microglia activation, reactive astrogliosis, and iNOS oxidative stress when compared to vehicle-treated littermates. This effect was dose-dependent, with 200 μg/g body weight as the optimal dose-regimen, and was maintained when curcumin treatment was delayed by 60 or 120 min post-HI. Cell proliferation measurements showed no changes between curcumin and HI alone, suggesting that the protective effects of curcumin on the neonatal brain following HI are most likely due to curcumin's anti-inflammatory and antioxidant properties, as seen in the reduced glial and iNOS activity. In conclusion, this study suggests curcumin as a potent neuroprotective agent with potential for the treatment of HIE. The delayed application of curcumin further increases its clinical relevance.

Any disease affects the psychological or mental state of the patient. The ailment caused by the lack of an insulin hormone is not considered an exception. Diabetes mellitus is also characterized by the presence of its psychosomatic abnormalities from the norm of development, which lead to a variety of disorders. Organic brain damage that occurs as a result of acute cerebral circulation disorders due to diabetes mellitus, and their consequences, tend to grow all over the world. A high incidence of strokes is due to a number of negative factors: hypertension, smoking, diabetes, hyperlipidemia, obesity, arthritically fibrillation, and others. The importance of climatic and geophysical factors in the development of vascular pathology has also been established. In addition, the percentage of patients with this disease of working age is growing. The psychosomatics of any disease that affects the endocrine system is hidden in serious disorders of nervous regulation. This is evidenced by clinical symptoms, including shock and neurotic states, depression and so on. However, these conditions can also become a major cause of the development of type 1 and type 2 diabetes. We pay special attention to verbal disorders in patients with diabetes mellitus.

Benzodiazepines are psychoactive drugs and some of them also affect immune cells. We
here characterized the inflammatory and infiltrating immune cells in the central nervous
system (CNS) during the acute phase of experimental autoimmune encephalomyelitis
(EAE) in animals treated with Diazepam. Also, we evaluated the expression of
Translocator Protein (18kDa) (TSPO), which is a biomarker of neuroinflammatory
diseases. The results indicate that Diazepam exerts protective effects on EAE
development, decreasing the incidence of the disease and reducing the number of
inflammatory cells in CNS, with a concomitant decrease of TSPO levels in brain tissue
and CNS inflammatory CD11b+ cells.

Intranasal insulin (INI) has been shown to modulate food intake and food related activity in the central nervous system in humans. As INI increases cerebrospinal fluid insulin concentration, these effects have been postulated to be mediated via insulin action in the brain, although peripheral effects of insulin cannot be excluded. INI has been shown to lower plasma glucose in some studies but it is not known whether it regulates endogenous glucose production (EGP).To assess the role of INI in the regulation of EGP, 8 healthy men were studied in a single-blind, crossover study with 2 randomized visits (one with 40 IU INI and the other with intranasal placebo (INP) administration) 4 weeks apart. EGP was assessed under conditions of an arterial pancreatic clamp, with a primed, constant infusion of deuterated glucose and infusion of 20% dextrose as required to maintain euglycemia.Between 180 and 360 minutes after administration, INI significantly suppressed EGP by 35.6% compared to INP,...

It is well established that individuals with Down syndrome develop Alzheimer’s disease neuropathology by middle age. Both in Alzheimer’s disease and Down syndrome, this is accompanied by the atrophy of NGF-dependent cholinergic neurons of the basal forebrain. An NGF trophic compromise in Alzheimer’s disease had been early suspected. This hypothesis was discarded with the finding of unaltered NGF mRNA synthesis and of increased NGF precursor levels (proNGF) in postmortem Alzheimer’s disease brains. The possibility of an NGF trophic disconnection has been recently revisited at the light of a newly discovered extracellular NGF metabolic pathway; where proNGF is released in an activity-dependent manner and converted by plasmin to mature NGF in the extracellular space. Mature NGF is ultimately degraded by the metalloprotease MMP-9. This pathway has been shown to be compromised in Alzheimer’s disease and Down syndrome brains, thus reviving the trophic factor hypothesis to explain the atrophy of basal forebrain cholinergic neurons in these disorders. This chapter will discuss the physiological role of NGF and its biological significance to cholinergic neurons of the CNS, and present the evidence for a dysregulation of the NGF metabolism in Alzheimer’s disease and Down syndrome.

We are taking an in vitro approach to study the effect of inflammatory mediators on cells in the rat central nervous system (CNS) and to assess their contribution (particularly microglia and astrocytes) to the inflammatory response. To this end, a three-dimensional aggregate culture system derived from foetal rat brain tissue which approximates to the brain in vivo in terms of glial and neuronal development and cell–cell interactions is used as a model of the CNS parenchyma.
Aggregate cultures are established by seeding dissociated foetal rat brain cells (Sprague–Dawley embryos at 16-days’ gestation) over agar to prevent adherence. Under these conditions, the cells form floating aggregates, which can be cultured for up to 6 weeks. Proliferating cells, identified by Bromodeoxyuridine (BrdU) incorporation and double labelling, include GFAP+ astrocytes. Basal levels of MHC classes I and II and CR3 expression are very low, as determined by immunocytochemistry and confocal microscopy. Treatment of aggregates with IFN-gamma (48 h, 50 ng/ml) results in increased MHC class I and class II expression. Preliminary results will be presented to illustrate how aggregate culture of foetal brain cells can be used to assess the effect of inflammatory mediators on cells within a complex CNS environment, complementing existing studies on isolated cell populations and co-cultures.

Drug disposition across the blood ‐brain barrier is frequently determined by measuring the distribution coefficient of drug between brain and plasma in vivo or by predicting the distribution coefficient from in vitro experiments. To render the distribution coefficient between brain and plasma (B/P ratio) a useful parameter for lead optimisation, it needs to be complemented with a measure of brain tissue binding, because it has been shown that only the free concentration of a drug in the brain relates to its pharmacodynamics. Methods for assessing drug disposition and brain tissue binding were reviewed and a new concept of brain availability has been introduced. Drug availability in the brain is defined as the product of the B/P ratio and the unbound fraction of drug in the brain. An easily accessible brain efficacy scale is introduced based on the proposed brain availability. Brain efficacy is defined as the ratio of brain availability over the drug’s inhibition constant. This relat...