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.

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.

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.

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.

Ophthalmomyiasis: three cases from North India.

Three cases of external ophthalmomyiasis are reported here. The larvae were identified to be Oestrus ovis in two cases and Cochliomyia hominivorax in one. Two of the patients were immunocompetent while one was undergoing treatment for squamous cell carcinoma of eyelid. In the latter myiasis led to complete destruction of the eye.

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.

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.

Identification of lysine positive non-fermenting gram negative bacilli (Stenotrophomonas maltophilia and Burkholderia cepacia complex).

BACKGROUND: The Burkholderia cepacia complex (BCC) and Stenotrophomonas maltophilia are closely related groups of non-fermenting gram-negative bacilli (NFGNBs) having a similar spectrum of infections ranging from superficial to deep-seated and disseminated infections. Identification of these lysine decarboxylase-positive NFGNBs lags behind in most Indian laboratories. A simplified identification scheme was devised for these two pathogens that allowed us to isolate them with an increasing frequency at our tertiary care institute. MATERIALS AND METHODS: A simple five-tube conventional biochemical identification of these bacteria has been standardized. In the beginning, some of the isolates were confirmed from the International B. cepacia Working group, Belgium. Molecular identification and typing using recA polymerase chain reaction-restriction fragment length polymorphism was also standardized for BCC. For short-term preservation of BCC, an innovative method of preserving the bacteria in Robertson's cooked medium tubes kept in a domestic refrigerator was developed. RESULTS: Thirty-nine isolates of BCC isolates were obtained from various specimens (30 from blood cultures) and 22 S. maltophilia (13 blood cultures and 9 respiratory isolates) were isolated during the year 2007 alone. CONCLUSIONS: BCC and S. maltophilia can be identified with relative ease using a small battery of biochemical reactions. Use of simplified methods will allow greater recognition of their pathogenic potential and correct antimicrobials should be advised in other clinical laboratories and hospitals.

Cognitive and other behavioral effects of EGb 761 in animal models.

Extensive pre-clinical and clinical studies conducted over more than three decades have established that EGb 761 (definition see editorial) represents a polyvalent therapeutic principle that is useful in the therapy of mildly to moderately severe dementia and other cognitive disorders. Besides cognition, other emotional and affective aspects of brain function also seem to benefit from EGb 761 treatment. Extensive behavioural studies in experimental animals are generally in line with clinical data since cognition improvement, stress protection, and antidepressive effects have been identified with this extract in proper animal models. While individual effects in all areas have been reported for adult animals and acute dosing, more pronounced effects are usually seen in aged animals and after subchronic treatment. Specifically, for the cognition improving properties pronounced beneficial effects are mainly present in those situations where cognition was impaired by aging or other noxious stimuli. Since all these conditions are associated with mitochondrial dysfunction, the stabilizing or even protecting effect of EGb 761 on mitochondrial function seems to be a major mechanism associated with many of EGb 761's behavioural effects. Bilobalide is most important in this respect. Moreover, bilobalide and the ginkgolides have recently been shown to affect chloride conductance by interfering with the function of membrane proteins related to receptor-gated chloride channels. These mechanisms are probably associated with behavioural effects requiring acute changes of neuronal activity, but might indirectly also improve mitochondrial function.

Structure-activity studies with Ginkgo biloba extract constituents as receptor-gated chloride channel blockers and modulators.

The constituents of Ginkgo biloba leaf extract, ginkgolides A, B, C and J are known as effective antagonists of platelet-activating factor (PAF). Here, we will demonstrate that these substances are also effective blockers of glycine-activated chloride channels in the hippocampal neurons of rat. As examined in several other voltage- and ligand-operated channels, this ginkgolide action is selective. The blocking action of all tested ginkgolides is use-dependent--they block open glycine-activated channels. The IC (50) values for saturating blocking action of ginkgolides B and C are 0.273 microM and 0.267 microM, respectively, while ginkgolides A and J are less effective--IC (50) values are 1.97 microM and 2.0 microM. Corresponding dose-response relationships are close to single-site binding isotherms. Another constituent of EGb 761, bilobalide, is a weak inhibitor of NMDA receptor-activated current. Its synthetic analogue, NV-31, demonstrates a weak facilitatory action on Gly-activated conductance. Novel findings have indicated the possibility that the unique modulating activity profiles of the EGb 761 (definition see editorial) constituents examined are due to their effects on the anion homeostasis of central neurons.

Excitotoxic hippocampal membrane breakdown and its inhibition by bilobalide: role of chloride fluxes.

We have previously shown that hypoxia and N-methyl-D-aspartate (NMDA) receptor activation induce breakdown of choline-containing phospholipids in rat hippocampus, a process which is mediated by calcium influx and phospholipase A (2) activation. Bilobalide, a constituent of Ginkgo biloba, inhibited this process in a potent manner (Weichel et al., Naunyn-Schmiedeberg's Arch. Pharmacol. 360, 609-615, 1999). In this study, we used fluorescence microscopy and radioactive flux measurements to show that bilobalide does not interfere with NMDA-induced calcium influx. Instead, bilobalide seems to inhibit NMDA-induced fluxes of chloride ions through ligand-operated chloride channels. In our experiments, substitution of chloride in the superfusion medium fully blocked the effect of NMDA on choline release from hippocampal slices, while the presence of chloride transport inhibitors (furosemide, DIDS) was partially antagonistic. The inhibitory effect of bilobalide and of HA-966, a glycine B receptor antagonist, on NMDA-induced choline release was attenuated in the presence of glycine. The inhibitory effect of bilobalide, but not that of HA-966, was also antagonized by GABA. The inhibitory effect of MK-801, an NMDA channel blocker, on choline release was insensitive to glycine. We conclude from our findings that bilobalide inhibits an NMDA-induced chloride flux through glycine/GABA-operated channels, thereby preventing NMDA-induced breakdown of membrane phospholipids. This effect is expected to contribute to the neuroprotective effects of ginkgo biloba extracts.

Effects of bilobalide on amino acid release and electrophysiology of cortical slices.

This study investigated the effects of bilobalide, a constituent of Ginkgo biloba, on potassium and veratridine-induced release of glutamate and aspartate from mouse cortical slices. We also studied its effects on spontaneous and N-methyl-D-aspartate (NMDA)-induced depolarizations elicited in magnesium-free artificial cerebrospinal fluid (aCSF) as well as its effect on NO-711 (a gamma-aminobutyric acid (GABA) uptake inhibitor)-induced depolarizations. Bilobalide, 100 microM significantly reduced both glutamate and aspartate release elicited by potassium or veratridine. Bilobalide (5-100 microM) also significantly reduced the frequency of NO-711 induced depolarizations, however, it had no effect on spontaneous or on NMDA-induced depolarizations at 5-200 microM. These results suggest that the neuroactive properties of bilobalide may be mediated by a reduction in excitatory amino acid neurotransmitter release.

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.

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).

Stimulation of glutamate, aspartate and gamma-aminobutyric acid release from synaptosomes by hyperforin.

Hyperforin is one pharmacologically active constituent of the medicinal herb Hypericum perforatum. The mechanism of its antidepressant-like activity is currently considered to be the inhibition of synaptic reuptake of neurotransmitters. Here, we will demonstrate that it also stimulates the release of glutamate from rat cortical synaptosomes, and that this effect is preceded by an increase in their free calcium [Ca2+]i levels. These hyperforin-related effects were also observed in the absence of Ca2+ in the medium. Although we noted enhanced glutamate, aspartate and GABA release under the influence of hyperforin, the release of various other amino acids was not enhanced. In contrast, reserpine did not influence the release of any of the amino acids studied. Adding hyperforin to synaptosomal suspension decreased their pHi, which returned to basal levels under certain incubation conditions. It also prevented the generation of ATP-induced pH gradients of isolated synaptic vesicles, and preformed pH-gradients were reversed by it. We will discuss the implications of our studies in understanding the mechanisms of hyperforin activity in relation to current findings on its pharmacological activity profile. Our observations suggest that neurotransmitter release stimulation from synaptosomes and the previously reported reuptake inhibitory properties of hyperforin are consequences of its effects on synaptosomal ionic homeostasis, and that it is not a reserpine-like agent.