Stress-Induced Haematohidrosis: a Case Report.

We describe a case of stress-induced haematohidrosis in a 14-year-old boy who responded well to stress management together with sertraline medication.

COVID-19 pandemic: mental health and beyond - the Indian perspective.

India is a de facto continent in the garb of a country. COVID-19 is an unprecedented global pandemic spanning continents. Being the second most populous country in the world, experts regard how India deals with the outbreak will have enormous impact on the world's ability to deal with it. The country has been in lockdown since March 25, 2020 until the current time of early May 2020, and despite several challenges, there has been early success. The major conflict now is the health benefits weighed up against the deleterious social and economic consequences of prolonged lockdown, that is, life versus livelihood. This unprecedented calamity could potentially cause or exacerbate various psychiatric disorders. It is recognized that lifestyle changes and limited screen time may help reduce mental health difficulties. Considering the physical barriers to consultation, development of telemedicine services is needed. This pandemic, like other previous pandemics, will pass, and until this happens, we must remain extremely vigilant.

Simple 2,4-diacylphloroglucinols as classic transient receptor potential-6 activators--identification of a novel pharmacophore.

The naturally occurring acylated phloroglucinol derivative hyperforin was recently identified as the first specific canonical transient receptor potential-6 (TRPC6) activator. Hyperforin is the major antidepressant component of St. John's wort, which mediates its antidepressant-like properties via TRPC6 channel activation. However, its pharmacophore moiety for activating TRPC6 channels is unknown. We hypothesized that the phloroglucinol moiety could be the essential pharmacophore of hyperforin and that its activity profile could be due to structural similarities with diacylglycerol (DAG), an endogenous nonselective activator of TRPC3, TRPC6, and TRPC7. Accordingly, a few 2-acyl and 2,4-diacylphloroglucinols were tested for their hyperforin-like activity profiles. We used a battery of experimental models to investigate all functional aspects of TRPC6 activation, including ion channel recordings, Ca(2+) imaging, neurite outgrowth, and inhibition of synaptosomal uptake. Phloroglucinol itself was inactive in all of our assays, which was also the case for 2-acylphloroglucinols. For TRPC6 activation, the presence of two symmetrically acyl-substitutions with appropriate alkyl chains in the phloroglucinol moiety seems to be an essential prerequisite. Potencies of these compounds in all assays were comparable with that of hyperforin for activating the TRPC6 channel. Finally, using structure-based modeling techniques, we suggest a binding mode for hyperforin to TRPC6. Based on this modeling approach, we propose that DAG is able to activate TRPC3, TRPC6, and TRPC7 because of higher flexibility within the chemical structure of DAG compared with the rather rigid structures of hyperforin and the 2,4-diacylphloroglucinol derivatives.

Percuteneous mitral balloon valvuloplasty in patients with post surgical mitral restenosis: result of 70 cases.

OBJECTIVE: To evaluate the immediate results of balloon mitral valvulplasty in mitral restenosis patients with previous surgical mitral commissurotomy. METHODS: Percuteneous balloon mitral valvuloplasty (BMV) was done in 145 cases of which 70patients had the history of previous surgical commissurotomy (Group I) and 75 patients were the new cases for the BMV (Group II). RESULTS: In group I the age range was 35-65 years. In group I the duration of surgical commissurotomy (SC) was of 2-18 years past. In this group the result of balloon mitral valvuloplasty (BMV) was successful in 69 cases. Mitral valve area (MVA) before the procedure was 0.5-0.9 sq cm with mean 0.7 +/- 0.2 sq cm. Following procedure the MVA was 1.2-2.0 cm2 with a mean of 1.6 +/- 0.4 cm2. Mean gradient across mitral valve (MV) before the procedure was 15-25 mm of Hg with a mean 20 +/- 5 mm of Hg and after the procedure was 3-5 mm Hg with a mean of 4 +/- 1 mm Hg. In Group I, MVA > 1.8 cm2 was achieved in 25 cases & > 1.2-1.8 cm2 in 44 cases. Mitral regurgitation > or = grade 1 occurred in 8 cases (compared to previous echocardiography). In group II the age range was between 35-60 years. The result of BMV was successful in 74 cases. MVA before the procedure was 0.4-1.2 cm2 with a mean of 0.8 +/- 0.4 cm2. Following the procedure MVA was 1.3-2.1 cm2 with a mean of 1.7 +/- 0.4 cm2. Mean gradient across the mitral valve before the procedure was 15-29 mm of Hg with a mean of 22 +/- 7 mm of Hg. Mean gradient across the mitral valve after the procedure was 2-4 mm of Hg with a mean of 3 +/- 1 mm of Hg. MVA more than 1.8 cm2 was achieved in 29 cases and between 1.3-1.8 in 45 cases. CONCLUSION: BMVin patients with mitral restenosis following Surgical mitral commissurtomy can be performed with almost similar success rate like that of BMV for the first time with low risk of major cardiac complication.

Validity of quantitative unspun urine microscopy, dipstick test leucocyte esterase and nitrite tests in rapidly diagnosing urinary tract infections.

OBJECTIVES: Rapid diagnostic tests can screen out negative samples and can save valuable time and money. The study was conducted to assess the usefulness of leukocyte esterase, nitrate reductase and quantitative microscopic unspun urine wet mount examination in rapidly diagnosing urinary tract infections (UTI). METHODS: Four hundred and fifty samples were tested by semi-quantitative culture on cysteine lactose electrolyte deficient medium, microscopic examination of unspun urine for significant pyuria, dipstick leucocyte esterase test (LET) and nitrite test (NT). Culture was used as gold standard to evaluate the performance of direct microscopy and dipstick tests. RESULTS: Urine culture examination revealed significant bacteriuria (>10(5) cfu/ml) 98 (21.8%), in urine samples. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the diagnostic odds ratio (DOR) of the dip-stick LET were 73.5%, 58.5%, 33.0%, 88.8%, and 3.9 respectively; those of the dip-stick NT were 57.1%, 78.7%, 42.7%, 86.8%, and 4.9 respectively; and those for microscopic significant pyuria detection were 68.4%, 60.8%, 32.7%, 87.3%, and 3.4 respectively. Highest sensitivity (95.9%), NPV (97.9%) and DOR (25.7) was obtained on combining microscopy and dip-stick LET and NT (either of them positive). This can potentially cut costs by 79%. CONCLUSION: Quantitative unspun urine wet mount microscopy and dipstick tests for leucocyte esterase and nitrite test should be added into routine laboratory practices for faster diagnosis of UTI.

Cardiological society of India document on safety measure during echo evaluation of cardiovascular disease in the time of COVID-19.

An echocardiographic investigation is one of the key modalities of diagnosis in cardiology. There has been a rising presence of cardiological comorbidities in patients positive for COVID-19. Hence, it is becoming extremely essential to look into the correct safety precautions, healthcare professionals must take while conducting an echo investigation. The decision matrix formulated for conducting an echocardiographic evaluation is based on presence or absence of cardiological comorbidity vis-à-vis positive, suspected or negative for COVID-19. The safety measures have been constructed keeping in mind the current safety precautions by WHO, CDC and MoHFW, India.

Cardiological Society of India: Document on acute MI care during COVID-19.

The unprecedented and rapidly spreading Coronavirus Disease-19 (COVID-19) pandemic has challenged public health care systems globally. Based on worldwide experience, India has initiated a nationwide lockdown to prevent the exponential surge of cases. During COVID-19, management of cardiovascular emergencies like acute Myocardial Infarction (MI) may be compromised. Cardiological Society of India (CSI) has ventured in this moment of crisis to evolve a consensus document for care of acute MI. However, this care should be individualized, based on local expertise and governmental advisories.

Invasive zygomycosis in India: experience in a tertiary care hospital.

AIM: To report the natural history and clinical course of zygomycosis from a single tertiary care centre in India where doctors maintain an institutional zygomycosis registry. METHODS: The clinical and laboratory data collected prospectively from patients with antemortem diagnosis for invasive zygomycosis, and retrospectively from autopsy diagnosed cases, over an 18 month period (July 2006-December 2007) were combined and analysed. RESULTS: During the period 75 cases (50 cases/year) of zygomycosis were reported. Antemortem diagnosis could be made in 81% of cases and 9% of patients had nosocomial zygomycosis. The spectrum of disease included rhino-orbito-cerebral (48%), pulmonary (17%), gastrointestinal (13%), cutaneous (11%), renal and disseminated zygomycosis (5% each). Uncontrolled type 2 diabetes (58%) and diabetic ketoacidosis (38%) in the rhino-orbito-cerebral type, renal failure (69%) in the pulmonary type, prematurity (70%) in the gastrointestinal type, and breach of skin (88%) in cutaneous zygomycosis, were the significant (p<0.05) underlying illnesses. Rhizopus oryzae (69%) was the most common isolate followed by Apophysomyces elegans (19%). Overall mortality was 45% in patients who could be treated. Outcome was significantly poor when surgical debridement could not be performed or the patients were treated only with amphotericin B deoxycholate. On multivariate analysis, patients with a Glasgow Coma Score (GCS) >or=9 had a better prognosis. CONCLUSIONS: Zygomycosis is a threat in uncontrolled diabetes. New risk factors such as renal failure and chronic liver disease require attention. A elegans is an emerging agent in India. The need for surgical debridement in addition to medical treatment is emphasised. GCS is an independent marker of prognosis in cases of invasive zygomycosis.

Nedocromil sodium is more effective than cromolyn sodium for the treatment of chronic reversible obstructive airway disease.

In a multicenter, double-blind, group comparative trial, the efficacy of nedocromil sodium (nedocromil, 4 mg, four times daily [qid]), cromolyn sodium (2 mg, qid), and placebo was compared in patients receiving inhaled beta 2-agonists and inhaled corticosteroids for the treatment of chronic reversible obstructive airway disease. After a 2-week baseline period, 132 patients (8 centers) between the ages of 20 and 75 years entered a 4-week run-in period in which the dose of inhaled corticosteroid was reduced by 50 percent. During the run-in phase, deterioration of symptoms (total symptom score) by ten points qualified patients to enter the 6-week drug trial period. Patients in the nedocromil treatment group showed the most robust and consistent improvements over placebo and cromolyn sodium for all daily dairy variables. Statistically significant improvements over placebo were noted for both active treatment groups for daytime, nighttime, and total symptom score. Symptom scores for nedocromil were statistically significantly improved over both cromolyn sodium and placebo for both daytime and nighttime asthma. Patients treated with nedocromil also demonstrated a significant reduction in the use of nighttime as needed (prn) beta 2-agonists as compared with either the placebo- or cromolyn sodium-treated groups. Only nedocromil-treated patients demonstrated a statistically significant improvement in morning peak expiratory flow rate (PEFR) as compared with placebo. Both nedocromil and cromolyn sodium groups demonstrated statistically significant improvements in afternoon and evening PEFRs. Collectively, the improvements in nighttime symptoms, decreased bronchodilator use, and improved morning PEFR show that patients treated with nedocromil had improved nocturnal symptoms. Pulmonary function tests (FEV1, FVC, PEFR) demonstrated no statistically significant differences between the two active treatments, although trends favored nedocromil for both FEV1 and PEFR. Although symptoms improved in patients treated with cromolyn sodium, the level of symptom control was less than that achieved by nedocromil. As compared with baseline control (regular dose of inhaled steroids), patients treated with nedocromil plus the 50 percent reduced dosage of inhaled corticosteroid consistently demonstrated comparable or better symptom control. Although both active drugs reduced symptoms, nedocromil proved to be more effective than cromolyn sodium for treatment of reversible obstructive airway disease in patients normally well maintained on regimens of low to moderate doses of inhaled corticosteroids.

The putative cognitive enhancer KA-672.HCl is an uncompetitive voltage-dependent NMDA receptor antagonist.

KA-672.HCl (KA-672) is a new substance demonstrating anti-dementia properties. It shows modulatory effects on several neurotransmitter systems known to be affected in patients with Alzheimer's disease. In this study the action of KA-672 on the NMDA receptors was examined by applying patch clamp techniques to acutely isolated hippocampal neurons. KA-672 antagonizes NMDA responses in a voltage-dependent manner. At a holding potential of -90 mV the IC50 value for the blocking action of KA-672 was 20+/-7 microM. This action of KA-672 is independent on the concentration either of agonist or coagonist of NMDA receptor. Ketamine, which interacts with the PCP center, does not occlude the action of KA-672. Evidently, KA-672.HCl is a weak NMDA receptor-operated channel blocker. This property may account for its pharmacological profile.

Phospholipid breakdown and choline release under hypoxic conditions: inhibition by bilobalide, a constituent of Ginkgo biloba.

A marked increase of choline release from rat hippocampal slices was observed when the slices were superfused with oxygen-free buffer, indicating hypoxia-induced hydrolysis of choline-containing phospholipids. This increase of choline release was suppressed by bilobalide, an ingredient of Ginkgo biloba, but not by a mixture of ginkgolides. The EC50 value for bilobalide was 0.38 microM. In ex vivo experiments, bilobalide also inhibited hypoxia-induced choline release when given p.o. in doses of 2-20 mg/kg 1 h prior to slice preparation. The half-maximum effect was observed with 6 mg/kg bilobalide. A similar effect was noted after p.o. administration of 200 mg/kg EGb 761, a ginkgo extract containing approximately 3% of bilobalide. We conclude that ginkgo extracts can suppress hypoxia-induced membrane breakdown in the brain, and that bilobalide is the active constituent for this effect.

The antiepileptic drug losigamone decreases the persistent Na+ current in rat hippocampal neurons.

The tetronic acid derivative losigamone is a new anticonvulsant drug with a mechanism of action that was previously unknown. The drug decreases the frequency of spontaneous action potentials and suppresses repetitive firing of neurons. Here we tested the hypothesis that losigamone suppresses the persistent Na+ current (I(NaP)) in hippocampal neurons of rat brain slices and in cultured hippocampal neurons. Whole-cell voltage clamp recordings from neurons of juvenile rats (P15-P25) were performed with pipettes filled with Cs-gluconate or CsF. After pharmacological block of K+ and Ca2+ currents I(NaP) was revealed by applying slow depolarizing voltage ramps from -70 to 0 mV. Losigamone (100-200 microM) was dissolved in DMSO (0.1%) and was applied by bath application or local pressure application. Losigamone induced a decrease in amplitude of I(NaP) at depolarized membrane potentials which was reversible in cultured neurons. When tetrodotoxin (TTX) was added to the bath, I(NaP) was blocked and only a residual non-specific outward cation current (I(cat)) remained. Losigamone had no obvious effect on responses to voltage ramps under these conditions. Thus, losigamone did not affect I(cat) or induce any additional currents. The data suggest that losigamone decreases neuronal excitability via a decrease in I(NaP).

Hyperforin enhances the extracellular concentrations of catecholamines, serotonin and glutamate in the rat locus coeruleus.

Hyperforin is the main antidepressant component of hypericum perforatum (St. John's Wort). Using the push-pull superfusion technique we tested whether hyperforin influences extracellular concentrations of neurotransmitters in the rat locus coeruleus. Hyperforin (10 mg/kg, i.p.) not only enhanced the extracellular levels of the monoamines dopamine, noradrenaline and serotonin, but also that of the excitatory amino acid glutamate. The levels of the main serotonin metabolite 5-hydroxyindolacetic acid, as well as those of the amino acids GABA, taurine, aspartate, serine and arginine, were not influenced. Together with in vitro studies, our findings suggest that the antidepressant property of hyperforin is due to enhanced concentrations of monoamines and glutamate in the synaptic cleft, probably as a consequence of uptake inhibition.

KA-672 inhibits rat brain acetylcholinesterase in vitro but not in vivo.

KA-672, a lipophilic benzopyranone derivative which is currently under development as a cognitive enhancer and antidementia drug, has previously been shown to have facilitatory effects on learning and memory in rats at doses of 0.1-1 mg/kg. We now report that KA-672 inhibited the activity of acetylcholinesterase (AChE), measured in vitro in rat brain cortical homogenate, with an IC50 value of 0.36 microM indicating that KA-672 may improve cognitive functions as a consequence of AChE inhibition. However, when we employed the microdialysis procedure to monitor acetylcholine (ACh) release from rat hippocampus, no effect of KA-672 (0.1-10 mg/kg) was found, indicating a lack of inhibition of brain AChE under in vivo-conditions. [14C]-labelled KA-672 was found to easily penetrate the blood-brain barrier, and an apparent concentration of 0.22 nmol/g brain (equivalent to 0.39 microM tissue concentration) was calculated following an i.p. injection of 1 mg/kg KA-672. However, no labelled substance could be detected in hippocampal microdialysates or in cerebrospinal fluid (CSF) taken from the cisterna magna, indicating that the concentration of KA-672 in brain extracellular fluid must have been below 0.01 microM. We conclude that KA-672 is a potent AChE inhibitor, an activity which, however, does not contribute to its behavioural effects in vivo because the lipophilic drug does not reach sufficient concentrations in the extracellular fluid, apparently due to cellular sequestration.

Acute effect of KA-672, a putative cognitive enhancer, on neurotransmitter receptor binding in mouse brain.

7-Methoxy-6-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propoxy]-3,4-dim ethyl-2H-1-benzopyran-2-one hydro-chloride (KA-672), structurally related to naturally occurring coumarins, has been described as a potential drug for enhancing cognitive functions. However, a detailed characterization of the pharmacological profile of KA-672 in vivo is still lacking. Quantitative neurotransmitter receptor autoradiography was used as a tool to screen for KA-672-induced changes in a number of transmitter receptors including cholinergic, noradrenergic, glutamatergic, GABAergic, and serotonergic subtypes throughout the brain. Two hours following treatment of mice with 1 mg/kg KA-672 per os, slight increases of nicotinic and M1-muscarinic cholinergic receptor binding, of alpha2-and beta-adrenoceptor as well as 5-HT1A receptors in various cerebral cortical regions were observed, whereas 5-HT2A binding sites were strikingly increased throughout the brain following KA-672 treatment. In contrast, (+/-)-alphaamino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor binding was significantly decreased in some cortical regions after drug treatment. No effects of KA-672 treatment on N-methyl-D-aspartate, kainate, GABA(A) and benzodiazepine receptor as well as M2-muscarinic cholinergic and high-affinity choline uptake binding were observed. As interactions between the cholinergic, noradrenergic and serotonergic neurotransmission have been stressed to play important roles in realizing learning and memory events, the cognition-enhancing effects of KA-672 may be due to this complex in vivo pharmacological profile of KA-672.

A comparative trial of combination therapy in obstructive airways disease.

Eleven patients suffering from chronic reversible airways obstruction completed a comparative crossover trial of two combinations of a controlled-release aminophylline formulation and inhaled salbutamol, and two combinations of oral and inhaled salbutamol. Assessment was by FEV1, which was measured at the end of each 2-week treatment period. The highest mean FEV1 was recorded in patients using controlled-release aminophylline plus routine inhaled salbutamol. The only treatment which gave a significant (p < 0.05) increase over baseline was a combination of controlled-release aminophylline and inhaled salbutamol on demand. The combination of controlled-release aminophylline plus inhaled salbutamol on need was significantly more effective than the combination of oral salbutamol plus routinely inhaled salbutamol.

Comparative study of the effects of intravenous administration of aminophylline, salbutamol and terbutaline in patients suffering from reversible airways obstruction.

A study was carried out in 20 patients with reversible airways obstruction to compare the bronchodilator potency of salbutamol (250 micrograms), terbutaline (500 micrograms) and aminophylline (250 mg), given by slow intravenous injection. Patients received each of the three treatments, on separate days, in random order using a double-blind design. Measurements were made of pulmonary function, pulse rate and blood pressure and side-effects were recorded before and at intervals up to 4 hours after drug administration. All three drugs improved pulmonary function to a significant degree and this effect was observed at 5 minutes post-treatment and lasted for 3 hours. Terbutaline and salbutamol had a significantly greater effect than aminophylline, but there was no difference between salbutamol and terbutaline. Both salbutamol and terbutaline produced tachycardia of a similar magnitude, and which returned to initial values within 90 minutes post-injection. Aminophylline did not cause tachycardia and this difference compared with the beta-agonists on pulse rate was statistically significant (p less than 0.001). Salbutamol caused a significantly greater incidence of palpitations than did either aminophylline (p less than 0.01) or terbutaline (p less than 0.05). No other differences between treatments were observed.

A therapeutic comparison of ipratropium bromide and salbutamol in asthmatic patients.

A single-blind, crossover study was carried out in 43 asthmatic patients to compare the efficacy and tolerance of inhaled ipratropium bromide with inhaled salbutamol. One or other drug was given 3-times daily (0.04 mg ipratropium bromide or 0.2 mg salbutamol per dose) over a period of 4 weeks. Patients were then crossed over to the alternative medication for a further 4 weeks. The results of lung function tests performed at routine clinic visits and by the patients at home showed similar increases in peak flow and spirometry recordings, although more patients expressed a preference for salbutamol. Unwanted effects were minor with both drugs. It is suggested, therefore, that ipratropium bromide may be a useful alternative to beta-stimulants in some asthmatics.

St John's wort (Hypericum perforatum) modulates evoked potentials in guinea pig hippocampal slices via AMPA and GABA receptors.

The effects of an ethanolic extract of the plant Hypericum perforatum L. (St John's wort) (HYP) and its hydrosoluble fraction (HYPWS) on electrically evoked population spikes and fEPSP were investigated in this study. Concentration dependent (10(-6) to 10(-4) g/l) excitatory effects were found. Above concentrations of 10(-3) g/l, HYP reduced the evoked responses, whereas HYPWS further increased them. Paired pulse facilitation was unaffected with HYPWS (10(-4) to 10(-2) g/l). The excitatory effects of HYPWS were amplified by the GABA(A) and GABA(B) receptor antagonists bicuculline and phaclofen, respectively. These excitations were antagonised by the AMPA receptor antagonist CNQX. Excitations caused by hypericum were not antagonised by the NMDA receptor antagonists D-APV and MK801, the metabotropic glutamate receptor (type I and II) antagonist MCPG, or the L-type calcium channel blocker verapamil. Hypericin and hyperforin, two components of H. perforatum, were found not to be responsible for the excitatory effects of the extract.

Comparison of the effects of losigamone and its isomers on maximal electroshock induced convulsions in mice and on three different patterns of low magnesium induced epileptiform activity in slices of the rat temporal cortex.

Losigamone (AO-33) is a recemate of a tetronic acid derivative. The effects of losigamone and its three isomers (AO-242, AO-294 and AO-23) were compared on maximal electroshock (MES) induced convulsions in mice and on different patterns of extracellularly recorded, low Mg2+ induced epileptiform activity in slices of the rat temporal cortex. Lowering Mg2+ induced recurrent short discharges in areas CA3 and CA1 while ictaform events that lasted for many seconds were induced in the entorhinal cortex. In the hippocampus the activity stayed stable over a number of hours. In contrast, the ictaform events in the entorhinal cortex changed their characteristics after one to two hours to recurrent discharges of 0.8 to 10 s. Afterdischarges and interictal events were absent. 50 microM AO-242 showed a similar efficacy to 50 microM AO-33 in reducing and blocking epileptiform discharges in areas CA1 and CA3 while 50 microM AO-294 and 50 microM AO-23 had weaker effects than 50 microM AO-33. Concentrations of 50 microM and 100 microM AO-242 showed a similar efficacy to AO-33 on ictaform events in the entorhinal cortex. Late recurrent discharges were also blocked by AO-33 and AO-242 although at higher concentrations (300 microM). The in vitro observations are with respect to order of efficacy in accordance with the in vivo data obtained in the maximal electroshock test in mice. The order of potency in the MES test was AO-242 greater than AO-33 much greater than AO-294 much greater than AO-23.(ABSTRACT TRUNCATED AT 250 WORDS)