Exploring the Therapeutic Potential of Traditional Antimalarial and Antidengue Plants: A Mechanistic Perspective.

Malaria, a highly perilous infectious disease, impacted approximately 230 million individuals globally in 2019. Mosquitoes, vectors of over 10% of worldwide diseases, pose a significant public health menace. The pressing need for novel antimalarial drugs arises due to the imminent threat faced by nearly 40% of the global population and the escalating resistance of parasites to current treatments. This study comprehensively addresses prevalent parasitic and viral illnesses transmitted by mosquitoes, leading to the annual symptomatic infections of 400 million individuals, placing 100 million at constant risk of contracting these diseases. Extensive investigations underscore the pivotal role of traditional plants as rich sources for pioneering pharmaceuticals. The latter half of this century witnessed the ascent of bioactive compounds within traditional medicine, laying the foundation for modern therapeutic breakthroughs. Herbal medicine, notably influential in underdeveloped or developing nations, remains an essential healthcare resource. Traditional Indian medical systems such as Ayurveda, Siddha, and Unani, with a history of successful outcomes, highlight the potential of these methodologies. Current scrutiny of Indian medicinal herbs reveals their promise as cutting-edge drug reservoirs. The propensity of plant-derived compounds to interact with biological receptors positions them as prime candidates for drug development. Yet, a comprehensive perspective is crucial. While this study underscores the promise of plant-based compounds as therapeutic agents against malaria and dengue fever, acknowledging the intricate complexities of drug development and the challenges therein are imperative. The journey from traditional remedies to contemporary medical applications is multifaceted and warrants prudent consideration. This research aspires to offer invaluable insights into the management of malaria and dengue fever. By unveiling plant-based compounds with potential antimalarial and antiviral properties, this study aims to contribute to disease control. In pursuit of this goal, a thorough understanding of the mechanistic foundations of traditional antimalarial and antidengue plants opens doors to novel therapeutic avenues.

Biosynthesis and extrinsic toxicity of copper oxide nanoparticles against cattle parasites: An eco-friendly approach.

Plant extracts' ability to collect metals and decrease metal ions makes them a superior candidate for the biosynthesis of nanoparticles; hence, they are referred to as bio-nano factories since both living and dead dried biomass are employed to produce metallic nanoparticles. The antiparasitic activity of biosynthesized copper oxide nanoparticles (CuO NPs) was examined against cow tick larvae (Rhipicephalus microplus, Haemaphysalis bispinosa, and Hippobosca maculata). These parasitic larvae were treated with various concentrations of methanolic leaf extract of A. marmelos (MLE-AM) and biosynthesized CuO NPs for 24 h. CuO NPs were synthesized quickly using A. marmelos leaf extract, and nanoparticle synthesis was identified within 15 min. The results from characteristic XRD, FTIR, SEM, EDX, and TEM analyses confirmed the biosynthesis of CuO NPs. The presence of 26-Hydroxycholesterol was discovered as the predominant chemical present in the GC-MS analysis of MLE-AM. The maximum efficacy was observed in biosynthesized CuO NPs against R. microplus larvae, H. bispinosa adults, and Hip. maculata larvae (LC50 = 4.30, 9.50, and 11.13 mg/L; and LC90 = 8.30, 19.57, and 21.65 mg/L; and 6.219, 6.547, and 2.587). Overall, the bio-fabrication of CuO NPs has the potential to develop better and safer antiparasitic control techniques.

Clinical Pharmacokinetic Drug Interaction Potential of MenoAct851 in Adult, Female Healthy Volunteers.

BACKGROUND: MenoAct851 (Varanasi BioResearch Pvt. Ltd., Varanasi, India) is a patented polyherbal formulation developed to manage menopause symptoms that can be taken along with other allopathic medicines. OBJECTIVE: The present study aims to evaluate the drug interaction potential of MenoAct851 to inhibit cytochrome (CY) P450 in vitro in rats, and to measure its effects on simvastatin pharmacokinetic parameters in healthy human volunteers. METHODS: CYP450-carbon monoxide assay of MenoAct851 was performed in rat liver microsomes to calculate the percentage inhibition. Fluorometric assays of CYP3A4 and CYP2D6 determined half maximal inhibitory concentration value. A double-blind, randomized, placebo-controlled drug interaction study of MenoAct851 was conducted in 24 healthy adult female volunteers aged 25 to 50 years. The selected volunteers were randomized to receive placebo or MenoAct851 500 mg BID PO for 14 days. On the 15th day, each group received 40 mg single-dose simvastatin. Blood samples were drawn at different intervals to measure simvastatin pharmacokinetic parameters. RESULTS: The mean (SD) CYP450 concentration of the diluted microsome sample was calculated and found to be 0.405 (0.12) nmol/mg. The inhibitory potential of MenoAct851 (41.16% [1.24%]) was found to be less than ketoconazole. Half maximal inhibitory concentration values of MenoAct851 on CYP3A4 and CYP2D6 were 11.96 (1.04) µg/mL and 15.24 (0.58) µg/mL, respectively, but they were higher than respective positive controls. There was no statistically significant difference between MenoAct851 and placebo groups concerning the pharmacokinetic parameters such as Cmax, Tmax, t½, and mean residence time of simvastatin; however, AUC showed a significant difference (P < 0.05) between the groups. CONCLUSIONS: MenoAct851 produced weaker interaction potential with CYP3A4 and CYP2D6 substrates based on in vitro assays, but the findings of clinical pharmacokinetic analysis indicate that MenoAct851 increased the AUC of simvastatin and simvastatin hydroxy acid. Therefore, coadministration of MenoAct851 might lead to drug-herb interaction, thereby affecting the therapeutic effect of CYP3A4 substrates. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Luteinizing hormone beta gene polymorphism and its effect on semen quality traits and luteinizing hormone concentrations in Murrah buffalo bulls.

OBJECTIVE: Present investigation was aimed to study the Single Nucleotide Variants of the luteinizing hormone beta (LHß) gene and to analyze their association with the semen quality (fresh and post-thawed frozen semen) and luteinizing hormone (LH) concentrations in Murrah buffalo bulls. METHODS: Polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) and Sanger sequencing method is used to study genetic variability in LHß gene. LH assay was carried out using enzyme-linked immunosorbent assay method. A fixed general linear model was used to analyze association of single nucleotide polymorphism (SNP) of LHß gene with semen quality in 109 and LH concentrations in 80 Murrah bulls. RESULTS: LHß gene was found to be polymorphic. Total six SNPs were identified in LHß gene g C356090A, g C356113T, g A356701G, g G355869A, g G356330C, and g G356606T. Single Stranded Conformational Polymorphism variants of pattern 2 of exon 1+pattern 2 of exon 2+pattern 1 of exon 3 had highly significant (p<0.01) effect on sperm concentration (million/mL), percent mass motility, acrosome integrity and membrane integrity in fresh and frozen semen whereas significant (p<0.05) effect was observed on percent live spermatozoa. SSCP variants of pattern 2 of exon 1+pattern 2 of exon 2+pattern 1 of exon 3 had highly significant (p<0.01) effect on luteinizing hormone concentrations too. CONCLUSION: The observed association between SSCP variants of LHß gene with semen quality parameters and LH concentrations indicated the possibilities of using LHß as a candidate gene for identification of markers for semen quality traits and LH concentrations in Murrah buffaloes.

Pregabalin and lamotrigine in central poststroke pain: A pilot study.

BACKGROUND: Comparative study of Class I drugs in central poststroke pain (CPSP) is lacking. OBJECTIVE: To evaluate the safety and efficacy of pregabalin and lamotrigine in patients with CPSP. SETTING: Tertiary care teaching referral hospital. METHODS: We included consecutive patients with CPSP having ≥50 mm score on Visual Analog Scale (VAS) and randomized them to receive either oral pregabalin or oral lamotrigine. Their clinical findings, serum chemistry, and cranial magnetic resonance imaging findings were noted. The severity of CPSP was assessed by VAS while the allodynia was assessed on a 0-10 scale. The hospital anxiety and depression (HAD) score was also recorded. The primary outcome was> 50% reduction in the VAS score while the secondary outcome was> 50% reduction in the severity of allodynia and improvement in HAD score at 3 months. Adverse reactions were noted in both the groups. RESULTS: There were 30 patients with CPSP with a median age of 54.5 years (Male:Female = 36:4). While both pregabalin (P < 0.0001) and lamotrigine (P < 0.0001) resulted in significant improvement in the VAS score (63.3% vs. 53.3%), allodynia (66.7% vs. 75%), and HAD score (80% vs. 81.8%) compared to the baseline, the was no significant intergroup difference. Lamotrigine had to be withdrawn in three patients due to skin rash. CONCLUSIONS: Both pregabalin and lamotrigine are equally effective in CPSP, but significant side effects leading to drug withdrawal occured with lamotrigine administration.

Reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for rapid diagnosis of chilli veinal mottle virus.

Chilli veinal mottle virus (ChiVMV) causes significant economic loss to chilli cultivation in northeastern India, as well as in eastern Asia. In this study, we have developed a single-tube one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for rapid, sensitive and specific diagnosis of ChiVMV. Amplification could be visualized after adding SYBR Green I (1000×) dye within 60 min under isothermal conditions at 63 °C, with a set of four primers designed based on the large nuclear inclusion protein (NIb) domain of ChiVMV (isolate KC-ML1). The RT-LAMP method was 100 times more sensitive than one-step reverse transcription polymerase chain reaction (RT-PCR), with a detection limit of 0.0001 ng of total RNA per reaction.

Clinical, nerve conduction and nerve biopsy study in vitamin B12 deficiency neurological syndrome with a short-term follow-up.

OBJECTIVE: The frequency and type of neuropathy in vitamin B12 deficiency neurological syndrome (VBDNS) is controversial. This study reports the frequency and type of nerve dysfunction in VBDNS using nerve conduction and sural nerve biopsy and its response to treatment. METHOD: Sixty-six patients with VBDNS diagnosed on the basis of low serum vitamin B12 level and/or megaloblastic bone marrow were subjected to clinical evaluation, hemoglobin, mean corpuscular volume, thyroid function test, HIV serology, and vasculitic profile. Peroneal motor and sural sensory nerve conduction studies were done. Sural nerve biopsy was done in six patients. The patients were treated with cyanocobalamin injection and followed up clinically and with nerve conduction study at 3 and 6 months. RESULTS: The median age of the patients was 46 (12-80) years and 11 patients were females. The duration of symptoms was 1-96 (median 7) months. Clinical features of neuropathy were present in 46 (69.7%) patients and nerve conduction was abnormal in 36 (54.5%) patients. On nerve conduction study, 8 (22.2%) patients had axonal, 4 (11.1%) had demyelinating, and 24 (66.7%) had mixed features. Nerve biopsy revealed acute axonal degeneration in early stage and chronic axonopathy with demyelination in the late stages of disease. The nerve conduction parameters improved at 6 months along with clinical recovery. CONCLUSION: Nearly 70% patients with VBDNS had evidence of neuropathy which is mainly axonal with some demyelinating features.

Worsening of Wilson disease following penicillamine therapy.

BACKGROUND: Penicillamine is a standard therapy for Wilson disease (WD) but some patients have paradoxical worsening. Predictors of such deterioration have not been evaluated. This study documents frequency and predictors of deterioration following treatment in WD. METHODS: 59 consecutive patients with neurologic WD and 4 asymptomatic siblings were prospectively evaluated. Their clinical, laboratory, ultrasound abdomen and cranial MRI findings with and without worsening were compared. Patients were treated with oral penicillamine and/or zinc and followed up at 1, 3 and 6 months or earlier if needed. Deterioration was defined by >10% worsening in baseline Burke-Fahn-Marsden score or appearance of new neurological sign. RESULTS: Patients' median age was 13 years and 13 were females. 19 patients (30.2%) worsened following treatment; 10 within 1 month, 7 in 1-3 months, and 2 after 3 months of treatment. Deterioration was associated with drooling, leukopenia, thrombocytopenia, splenomegaly and evidence of chronic liver disease. None of the asymptomatic patients following zinc therapy deteriorated. CONCLUSIONS: In the deteriorating group, withdrawal of penicillamine resulted in improvement/stabilization in 11 patients, 2 improved by trientine therapy and 4 continued to deteriorate till 3 months. 30.2% patients with WD deteriorated following penicillamine, especially those with chronic liver disease, leukopenia and thrombocytopenia.

Network pharmacology based pharmacokinetic assessment and evaluation of the therapeutic potential of catechin derivatives as a potential myostatin inhibitor: A special view on Sarcopenic Obesity.

Sarcopenic obesity has become a significant age-related metabolic problem. Catechins are flavanol, derivatives which poses a strong antioxidant activity. The major components of catechin derivatives. were identified through our physicochemical and pharmacokinetic parameters estimation. Therefore, in this study, network pharmacology was used to explore the multiple targets related to Sarcopenia, Metabolic syndrome, and obesity. The targets were identified from network analysis. The catechin derivatives were screened using Lipinski's rule of five, Veber scale, Egan scale, and Muegge scale. From this drugglikness property catechin and Epicatechin was selected which were docked towards the myostatin inhibition PDB ID: 3HH2. Furthermore, the computational docking method on Catechin and Epicatechin with the stronger interaction towards myostatin inhibition receptor with the binding energy of -6.90 kcal/mol. and -7.0 kcal/mol from autodock software, respectively, for catechin and Epicatechin. Higher binding energy confirms the pharmacotherapeutic activity of Catechin and Epicatechin toward the myostatin inhibitor target.

A Comparative Study of the Effectiveness and Safety of Topical Calcipotriol and Topical Methotrexate in Chronic Plaque Psoriasis.

Background Psoriasis is a papulosquamous disease with variable morphology, distribution, severity, and course. Chronic plaque psoriasis, or psoriasis vulgaris, is the most common form of psoriasis. Present available preparations for mild to moderate chronic plaque psoriasis for topical use are local corticosteroids, coal tar, dithranol, tazarotene, calcipotriol, tapinarof, and calcineurin inhibitors. However, every preparation has its disadvantages. Calcipotriol, an active form of vitamin D, is available in topical form for dermatological use. Chronic plaque psoriasis is the chief medical use of calcipotriol for mild to moderate form. Methotrexate has dramatic results in psoriasis when used systemically. Now, topical formulation is being advocated in localized psoriasis, which is not associated with the side effects of the systemic form. Therefore, this study aimed to compare the effectiveness of topical calcipotriol and topical methotrexate on the basis of the psoriasis area severity index (PASI) in patients of chronic plaque psoriasis and compare their safety in terms of adverse effects. Methodology The total number of patients included in the study was 60. They were divided into two groups, with 30 patients each. One group was prescribed ointment calcipotriol 0.005% twice daily local application (Group C). The other group was prescribed methotrexate gel 1% twice daily local application (Group M). The patients were followed up on the fourth and eighth weeks, and at each time, thorough clinical examinations were conducted for all patients. The PASI score was calculated in each patient every time. Safety was assessed by biochemical parameters, and tolerability was assessed by the incidence of adverse effects. All the patients included in the study were investigated at baseline, fourth week, and eighth week. The data collected were transferred to a master chart and analyzed. Results For the patients in group C, the mean PASI score at 0 week was 5.93 ± 2.62, while at four weeks, the mean PASI score declined to 1.67 ± 1.13, and at eight weeks, the mean PASI score further declined to 0.67 ± 0.68. For the patients in group M, the mean PASI score at 0 week was 5.91 ± 2.22, while at four weeks, the mean PASI score declined to 1.91 ± 1.11, and at eight weeks, the mean PASI score further declined to 0.89 ± 0.72. Furthermore, there was no significant difference in the mean PASI score at various time points when compared between the two groups (p-value = 0.761, 0.296, 0.079, respectively). Thus, both drugs seem to be effective in treating mild- to moderate-grade chronic plaque psoriasis. Most of the patients in both groups showed marked clearance of the lesions. However, there were six patients in the calcipotriol group showing complete clearance of the lesions having mild-degree plaque psoriasis, as compared to three patients in the methotrexate group. In the present study, based on the comparison of safety and tolerability, four out of 30 patients (13.3%) in the calcipotriol group suffered skin irritation, whereas six out of 30 patients (20%) in the methotrexate group complained of a burning sensation. The adverse effects seen in the patients were transient and mild. Conclusion Topical calcipotriol and methotrexate were effective in reducing lesions in patients with chronic mild to moderate plaque psoriasis. Both drugs were well tolerated with mild and transient adverse effects and did not alter hematological and biochemical parameters.

A study of neurobehavioral, clinical psychometric, and P3 changes in vitamin B12 deficiency neurological syndrome.

OBJECTIVE: To evaluate cognitive functions and behavioral changes in the patients with vitamin B12 deficiency neurological syndromes (VBDNS) using detailed clinical psychometric and P3 studies and their response to treatment. METHODS: The patients with VBDNS were included and their detailed medical history was recorded. Neurobehavioral and cognitive functions were evaluated by neuropsychiatry inventory (NPI), forward and backward digit span, mini mental state examination (MMSE), Luria's three-step test, trail making test (TMT), motor speed and precision test (MSPT), Benton's visual retention test (BVRT), clock drawing (CD), category fluency, hospital anxiety and depression (HAD) scale, and cognitive evoked potential using oddball paradigm at baseline and 3 and 6 months following treatment. Complete hemogram, serum chemistry, vitamin B12, homocysteine, and craniospinal magnetic resonance imaging (MRI) were done. RESULTS: Thirty-three patients with VBDNS, whose median age was 43 (12-68) years, five (15.2%) of whom were females were included. Twenty-one patients had neurobehavioral/cognitive decline, 26 myelopathy, and 17 neuropathy. MSPT, TMT, CD, and HAD scores improved significantly at 3 months and category naming and MMSE improved at 6 months compared to baseline. The P3 latency also improved significantly at 3 months. The baseline P3 changes correlated with MMSE, Luria's three-step test, and MSPT. Hemoglobin and mean corpuscular volume also correlated with some of the cognitive tests. CONCLUSION: VBDNS results in frontal-subcortical neurobehavioral and cognitive abnormalities which may be due to cortical and subcortical dysfunction. The reversibility of these changes is suggestive of metabolic alteration in neuronal or myelin function.

Association of antibiotics with status epilepticus.

The objective of this study is to evaluate clinical picture, radiological findings and response to treatment in patients with antibiotic associated status epilepticus (SE). In a retrospective review, 12 out of 117 (10%) patients with SE had temporal association with antibiotic administration. Their medical history, clinical findings, and duration and type of SE were recorded. Serum chemistry, blood counts, cranial MRI, EEG and CSF examination were carried out. The offending antibiotics were withdrawn and the patients were treated with phenytoin, lorazepam, sodium valproate or midazolam. The response to treatment was recorded and death during hospital stay noted. The median age of the patients was 36 (18 and 74) years and 5 were females. Eight patients had convulsive and four nonconvulsive SE. The median duration of status was 12 h. The antibiotics related to SE included intravenous cephalosporin (ceftazidime 5, amoxyclavulenic acid 2, piperacillin 2, cefepime 1) and quinolones (levofloxacin 3, ofloxacin 1, ciprofloxacin 2) in isolation or in combinations. Five patients had hepatic (41.7%) and 6 (50%) renal failure; the later received higher than the recommended dose of antibiotics. Cranial MRI was abnormal in 7 out of 9 (77.8%) patients that include cortical lesion in one, corticosubcortical in three and subcortical in three. SE responded to first antiepileptic drug in four and to second in five patients. Three patients (25%) had refractory SE. Eight (66.7%) patients died and death was related to SE in 2 patients. 10% SE patients may be related to antibiotics. Hence the antibiotic should be carefully chosen in patients with hepatic and renal failure, and the dose should be modified.

Prolificacy Assessment of Spermatozoan via State-of-the-Art Deep Learning Frameworks.

Childlessness or infertility among couples has become a global health concern. Due to the rise in infertility, couples are looking for medical supports to attain reproduction. This paper deals with diagnosing infertility among men and the major factor in diagnosing infertility among men is the Sperm Morphology Analysis (SMA). In this manuscript, we explore establishing deep learning frameworks to automate the classification problem in the fertilization of sperm cells. We investigate the performance of multiple state-of-the-art deep neural networks on the MHSMA dataset. The experimental results demonstrate that the deep learning-based framework outperforms human experts on sperm classification in terms of accuracy, throughput and reliability. We further analyse the sperm cell data by visualizing the feature activations of the deep learning models, providing a new perspective to understand the data. Finally, a comprehensive analysis is also demonstrated on the experimental results obtained and attributing them to pertinent reasons.

Comparative Assessment of Perceived Pain in Children During Palatal Anesthesia Using Two Injection Techniques: An In Vivo Study.

Background: Computer-controlled local anesthetic delivery (CCLAD) is an approach that uses a constant and slow flow of delivering the anesthetic solution into the tissues, which is capable of alleviating pain and discomfort in children. Aim: Assessment of perceived pain in children during palatal anesthesia using Wand technique and conventional technique. Materials and Methods: A total of 30 children requiring bilateral palatal anesthesia were included in the study in a split-half design. The children were asked to indicate their intensity of pain response on a visual analog scale (VAS) after administration of anesthesia by the Wand technique and the conventional technique. Statistical Analysis: The data were analyzed using Statistical Package for the Social Sciences (SPSS) 16.0. Mann-Whitney U test compared the mean VAS scores between the two groups. Statistical significance was defined as a P value of less than 0.05. Results: The mean VAS scores using the Wand technique and the conventional technique were 3.87 ± 1.99 and 4.20 ± 1.44, respectively (P = 0.332). Females had lesser VAS scores compared to males (P = 0.008). Conclusion: Females readily accepted the Wand technique compared to males, although there was no substantial difference between the two injection procedures.

Semantic Analysis and Topic Modelling of Web-Scrapped COVID-19 Tweet Corpora through Data Mining Methodologies.

The evolution of the coronavirus (COVID-19) disease took a toll on the social, healthcare, economic, and psychological prosperity of human beings. In the past couple of months, many organizations, individuals, and governments have adopted Twitter to convey their sentiments on COVID-19, the lockdown, the pandemic, and hashtags. This paper aims to analyze the psychological reactions and discourse of Twitter users related to COVID-19. In this experiment, Latent Dirichlet Allocation (LDA) has been used for topic modeling. In addition, a Bidirectional Long Short-Term Memory (BiLSTM) model and various classification techniques such as random forest, support vector machine, logistic regression, naive Bayes, decision tree, logistic regression with stochastic gradient descent optimizer, and majority voting classifier have been adapted for analyzing the polarity of sentiment. The effectiveness of the aforesaid approaches along with LDA modeling has been tested, validated, and compared with several benchmark datasets and on a newly generated dataset for analysis. To achieve better results, a dual dataset approach has been incorporated to determine the frequency of positive and negative tweets and word clouds, which helps to identify the most effective model for analyzing the corpora. The experimental result shows that the BiLSTM approach outperforms the other approaches with an accuracy of 96.7%.

An in vitro evaluation of radicular penetration of hydrogen peroxide from bleaching agents during intra-coronal tooth bleaching with an insight of biologic response.

OBJECTIVES: External root resorption is the complication of intra-coronal bleaching done with 30% H2O2 alone or mixed with sodium perborate but not with sodium perborate mixed with water. The study was done to comparatively evaluate the H2O2 leakage from three H2O2 liberating bleaching agents. STUDY DESIGN: Fifty one single rooted human teeth were used. After root canal therapy gutta percha was removed below cemento-enamel junction. Three bleaching agents: sodium perborate mixed with water, sodium perborate mixed with 30% H2O2 and 30% H2O2 alone were used. Teeth without defect, with cervical root defect and with mid root defect constituted group A, group B and group C. According to various bleaching agents groups were subdivided into subgroup 1, 2 and 3. H2O2 leakage was measured with the help of spectrophotometer RESULTS: Almost all teeth showed H2O2 leakage. It was maximum in B1 followed by C1, B2, A1, A2, C2, B3, A3 and C3. CONCLUSION: Sodium perborate mixed with water was found to be the best bleaching agent.

CYP3A4 mediated pharmacokinetics drug interaction potential of Maha-Yogaraj Gugglu and E, Z guggulsterone.

Maha yogaraja guggulu (MYG) is a classical herbomineral polyherbal formulation being widely used since centuries. The aim of this study was to investigate the effect of MYG formulation and its major constituents E & Z guggulsterone on CYP3A4 mediated metabolism. In vitro inhibition of MYG and Guggulsterone isomers on CYP3A4 was evaluated by high throughput fluorometric assay. Eighteen Adult male Sprague-Dawley rats (200 ± 25 g body weight) were randomly divided into three groups. Group A, Group B and Group C were treated with placebo, MYG and Standard E & Z guggulsterone for 14 days respectively by oral route. On 15th day, midazolam (5 mg/kg) was administered orally to all rats in each group. Blood samples (0.3 mL) were collected from the retro orbital vein at 0.25, 0.5, 0.75, 1, 2, 4, 6, 12 and 24 h of each rat were collected. The findings from the in vitro & in vivo study proposed that the MYG tablets and its guggulsterone isomers have drug interaction potential when consumed along with conventional drugs which are CYP3A4 substrates. In vivo pharmacokinetic drug interaction study of midazolam pointed out that the MYG tablets and guggulsterone isomers showed an inhibitory activity towards CYP3A4 which may have leads to clinically significant interactions.

Clonazepam responsive opsoclonus myoclonus syndrome: additional evidence in favour of fastigial nucleus disinhibition hypothesis?

Opsoclonus myoclonus syndrome is a rare paraneoplastic syndrome seen in 50% of children with neuroblastoma. Neural generator of opsoclonus and myoclonus is not known but evidences suggest the role of fastigial nucleus disinhibition from the loss of function of inhibitory (GABAergic) Purkinje cells in the cerebellum. We present a child with paraneoplastic opsoclonus myoclonus syndrome who responded well to clonazepam. Response to clonazepam is an evidence for the involvement of GABAergic neural circuits in the genesis of opsoclonus myoclonus syndrome and is in agreement with fastigial nucleus disinhibition hypothesis.

Comparative Study to Assess the Effectiveness of Topical Nifedipine and Diltiazem in the Treatment of Chronic Anal Fissure.

BACKGROUND: Chronic anal fissure is a common condition which is classically treated by surgery which may lead to incontinence. Recently medical treatment in form of calcium channel blockers (CCB) has gained interest. AIMS: The aim of this study is to compare the effectiveness of local Nifedipine and Diltiazem with lignocaine as control. We also aimed to observe the clinical pattern of chronic anal fissure. MATERIAL AND METHOD: Patients of chronic anal fissure were divided into three groups. First group received topical Nifedipine, second received topical Diltiazem, and the control group received only local lignocaine for 1 month. Their clinical data was recorded. The intensity of pain and bleeding was assessed from a visual analogue score (VAS). On the 4th week patients were examined for healing. STATISTICAL ANALYSIS: Statistical analysis was done by Medcalc statistical software v14. Student's t-test and Chi-square test was used accordingly. RESULTS: Mean age was 35.89 with a male female ratio of 1.7:1. Most common clinical feature was pain (100%), followed by constipation, bleeding, and pruritus. Most common location was posterior. VAS scores for pain of the Nifedipine group and Diltiazem group was significantly better than control group (P < 0.0001). VAS scores for bleeding in the Nifedipine group (P = 0.0091) and Diltiazem group (P = 0.0045) was significantly better than control group. The healing rate for NFD group was 93.33% (P < 0.0001), that of DTZ group was 86.67% (P = 0.0002), which was statistically better than control group (36.67%). There was no significant difference between the two CCBs. CONCLUSION: Adding topical Nifedipine or Diltiazem in the treatment of anal fissure is far superior to treatment with only topical Lignocaine.