Biomedical subjects
K R Murthy
Publications and source records attributed to K R Murthy.
Effect of Indian red scorpion (Mesobuthus tamulus concanesis, Pocock) venom on thyroxine and triiodothyronine in experimental acute myocarditis and its reversal by species specific antivenom.
Acute myocarditis was induced in dogs and rabbits by injection of scorpion (M. tamulus concanesis, earlier called Buthus tamulus) venom by s.c., i.m. or i.v. routes. A decrease in thyroxine (T4) levels was observed following i.v. injection of venom in dogs. In rabbits the venom (i.m.) did not elicit any change in T4 levels. Envenomation (s.c.) resulted in a reduction in triiodothyronine (T3) levels in dogs. Venom injection (s.c.) along with i.v. administration of the species specific antivenom (AScVS) did not cause any change in T3 and T4 levels in general. However an increase in T3 levels following AScVS was observed in envenomated dogs. The results suggest that scorpion envenomation caused an autonomic storm releasing massive amounts of catecholamines, angiotensin II, suppressed insulin secretion and reduced circulating T4 and T3 levels. Decrease in thyroid hormones results in fall in body temperature. Changes in the body temperature may increase the sensitivity of the scorpion venom and influence the course of toxicity.
Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy.
Autosomal recessive childhood-onset severe retinal dystrophy (arCSRD) designates a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously. The most severe cases are termed Leber congenital amaurosis (LCA), while the less aggressive forms are usually considered juvenile retinitis pigmentosa. Recently, mutations in the retinal-specific guanylate cyclase gene were found in patients with LCA. Disease genes implicated in other forms of arCSRD are expected to encode proteins present in the neuroretina or in the retinal pigment epithelium (RPE). The RPE, a monolayer of cells separating the vascular-rich choroid and the neuroretina, is in intimate contact with the outer segments of rods and cones via the microvilli surrounding the photoreceptors. The RPE expresses a tissue-specific and evolutionarily highly conserved 61 kD protein (RPE65) present at high levels in vivo. Although the function of RPE65 is not yet known, an important role in the RPE/photoreceptor vitamin-A cycle is suggested by the fact that RPE65 associates both with serum retinol-binding protein and with the RPE-specific 11-cis retinol dehydrogenase, an enzyme active in the synthesis of the visual pigment chromophore 11-cis retinal. Here we report that the analysis of RPE65 in a collection of about 100 unselected retinal-dystrophy patients of different ethnic origin revealed five that are likely to be pathogenic mutations, including a missense mutation (Pro363Thr), two point mutations affecting splicing (912 + 1G-->T and 65 + 5G-->A) and two small re-arrangements (ins144T and 831del8) on a total of nine alleles of five patients with arCSRD. In contrast to other genes whose defects have been implicated in degenerative retinopathies, RPE65 is the first disease gene in this group of inherited disorders that is expressed exclusively in the RPE, and may play a role in vitamin-A metabolism of the retina.
2-Aminofluorene bioactivation by human term placental peroxidase.
Earlier investigations from our laboratory demonstrated that human term placental peroxidase (HTPP) is capable of metabolism of xenobiotics and endogenous compounds. In this study, purified HTPP was found to bioactivate 2-aminofluorene (2-AF) in the presence of H2O2. 2-AF oxidation was studied spectrophotometrically while radiometry was employed to assess the bioactivation. The rate of oxidation and covalent binding to protein and DNA was dependent upon the pH of the reaction medium and the concentration of 2-AF, the enzyme, and H2O2. To observe maximal enzyme velocity of oxidation, the presence of 16.5 microM H2O2, 100 microM 2-AF, 37 micrograms of the enzyme protein/ml, and pH 7.2 was required. Under optimal assay conditions, the range of specific activity between 130 and 165 nmol of 2-AF oxidized/min/mg HTPP was observed. Using similar assay conditions, the magnitude of covalent binding of [3H]-2-AF to protein (BSA) and calf thymus DNA was found to be about 508 pmol bound/min/mg HTPP/mg BSA and 84 pmol bound/min/mg HTPP/mg DNA, respectively. Potassium cyanide and sodium azide, the known inhibitors of different peroxidases, significantly blocked both the oxidation and covalent binding of 2-AF in a dose dependent manner. These results strongly suggest that peroxidase may be one of the important pathways responsible for the bioactivation of arylamines in human term placenta.
Xenobiotic metabolism in humans during early pregnancy: peroxidase-mediated oxidation and bioactivation of 2-aminofluorene.
Arylamines such as 2-aminofluorene (2-AF) are known teratogens and transplacental carcinogens in laboratory animal species. Although exposure of women to arylamines is likely to occur during pregnancy, how these chemicals are metabolized by the enzymes from the human conceptual tissues is currently unknown. Highly purified preparations of peroxidase isolated from human intrauterine conceptual tissues at 8 weeks of gestation were used to study in vitro metabolism of 2-AF. The oxidation of 2-AF was examined spectrophotometrically whereas the bioactivation was assessed from the covalent binding to protein and DNA using [3H] 2-AF. Using guaiacol as a model substrate, the purified preparations of peroxidase used exhibited a specific activity of 15-20 micromol/min/mg protein. 2-AF oxidation was found to be enzymatic in nature. Kinetic data obtained under optimal assay conditions yielded a Km = 41 microM for 2-AF, 8.33 microM for H2O2, and a Vmax=1.2 micromol 2-AF oxidized/min/mg protein. Under optimal assay conditions, the covalent binding of reactive intermediates to protein and DNA (nmol equivalent/min/mg enzyme/mg bovine serum albumin or calf thymus DNA) was observed at the rate of about 3.75 +/- 0.39 and 1.90 +/- 0.11 respectively. A significant decline in the rate of both oxidation and bioactivation of 2-AF was observed in the presence of classical peroxidase inhibitors, KCN and NaN3.
Colour of the nucleus as a marker of nuclear hardness, diameter and central thickness.
Hundred and thirty patients, aged above 40 years, with senile cataract were examined. Age and colour were selected as the probable preoperative indicators of nuclear hardness. The lens material collected after manual extracapsular extraction was washed and the nucleus isolated. The diameter and central thickness of the nucleus were measured; the mean diameter and mean central thickness were 7.13 mm +/- 0.76 and 3.05 mm +/- 0.48, respectively. The hardness of the nucleus was measured with a lens guillotine designed by us. Regression analysis was applied to the parameters measured and these were compared with the colour and age. The parameters measured had the following relationship: Colour vs hardness (r value = 0.7569) (p < 0.001) Colour vs diameter (r value = 0.3962) (p < 0.001) Colour vs central thickness (r value = 0.4785) (p < 0.001) Age vs hardness (r value = -0.0499) (p > 0.05) Age vs diameter (r value = 0.0987) (p > 0.05) Age vs central thickness (r value = 0.1700) (p > 0.05) The values showed that colour had a statistically significant relationship with all the 3 parameters (p < 0.001), while age had no significant relationship with the same parameters. The results indicated that colour can be used more reliably to predict physical characteristics of the cataractous lens nucleus, the preoperative knowledge of which would help the surgeon in planning small-incision surgery including phacoemulsification.
Scorpion envenoming and the role of insulin.
Scorpion envenoming results in a severe autonomic storm with a massive release of catecholamines, increased angiotensin II and inhibition of insulin secretion. These hormonal alterations could be responsible for the pathogenesis of a variety of clinical manifestations. Under these conditions, scorpion envenoming essentially results in a syndrome of fuel-energy deficits and an inability to utilize the existing metabolic substrates by vital organs causing multi-organ system failure and death. Based on our animal experiments in which insulin administration reversed the metabolic and ECG changes induced by scorpion envenoming and treating the poisonous scorpion sting victims with insulin, we consider that insulin has a primary metabolic role in preventing and reversing the cardiovascular, haemodynamic, and neurological manifestations and pulmonary oedema induced by scorpion envenoming. The use of continuous infusion of regular crystalline insulin at the rate of 0.3 U/g glucose and glucose at the rate of 0.1 g/kg/hr, with supplementation of potassium as needed and maintenance of fluid electrolytes and acid-based balance, has become a routine protocol in our setting for treating the victims of scorpion envenoming.
Electromyographic analysis of standing posture and demi-plié in ballet and modern dancers.
Surface electromyography was used to analyze lower extremity muscle activity during standing posture and demi-plié in first position with lower extremities turned out, in five ballet and seven modern female professional dancers. In standing posture, increased electromyographic (EMG) activity above baseline was detected most frequently at the medial gastrocnemius (54% standing repetitions) and tibialis anterior (29%) electrodes (all dancers); in ballet dancers, increased EMG activity during standing was significantly less frequent at the medial gastrocnemius, but more frequent at the tibialis anterior, than in modern dancers. In demi-plié, the tibialis anterior had a discrete peak of EMG activity at midcycle in all dancers (97% demi-pliés). All dancers also had midcycle EMG activity in both vastus lateralis and medialis (100% demi-pliés). At the end of rising phase of demi-plié, ballet dancers had greater EMG activity than at midcycle in vastus lateralis (100% demi-pliés) and medialis (92%); in modern dancers, end-rising phase voltage was lower than at midcycle for vastus lateralis (71% demi-pliés) and medialis (83%). Genu recurvatum > or = 10 degrees was observed at the beginning and end of demi-plié in all ballet dancers, but not in modern dancers. There was marked variation of EMG activity during demi-plié in the lateral gastrocnemius, medial gastrocnemius, gluteus maximus, hamstrings, and adductors. The results support the hypothesis that ballet and modern dancers have different patterns of muscle use in standing posture and demi-plié, which in part may be a result of differences in genu recurvatum and turnout between the two groups.
Scorpion stings and role of insulin.
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Role of insulin in non-cardiac pulmonary oedema in scorpion stings.
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Insulin reverses haemodynamic changes and pulmonary oedema in children stung by the Indian red scorpion Mesobuthus tamulus concanesis, Pocock.
The efficacy of insulin administration in reversing haemodynamic changes in pulmonary oedema in victims of poisonous scorpion sting is assessed by a study based on animal experiments in which insulin administration reversed metabolic and electrocardiographic changes induced by scorpion envenomation. Six previously healthy children aged 18 months to 11 years were admitted to hospital five to 17 hours after scorpion sting. Frusemide for raised central venous pressure and pulmonary oedema, crystalloid infusion for reduced central venous pressure, and hydrocortisone and dopamine for hypotension were used as standard therapy. Insulin (0.3 units g-1 of glucose) was administered when the standard therapy failed to produce an improvement, and at the earliest sign of haemodynamic instability. Reversal of pulmonary oedema and haemodynamic changes, and attainment or normal respiratory rate, blood pressure and central venous pressure, were observed. It is concluded that insulin administration may be useful in reversing haemodynamic changes and pulmonary oedema in victims of scorpion stings.
The effects of external bending moments on lumbar muscle force distribution.
A detailed biomechanical model of the low-back musculature that predicts muscle-force distribution in response to external loading is presented. The paper shows that the class of loading tasks that involve an erect posture and an arbitrary load placed on the upper limbs can be described as a loading plane whose axes are the flexion and lateral bending moments. Under these conditions, the individual muscle forces are described as a three-dimensional surface defined by the loading plane and termed the muscle activity surface (MAS). The MAS and the loading plane intersect along the switching curve which separates the load combinations that activate the muscle from those that do not. The paper suggests the existence of a recruitment order of low back muscles in response to external loads and presents a comprehensive framework for examining earlier studies that used EMG measurements to validate physiological and mechanical predictions.
1989 Volvo Award in biomechanics. Mechanical recruitment of low-back muscles. Theoretical predictions and experimental validation.
A biomechanical model for studying lumbar muscle load sharing for a class of physical tasks that involve gravitational loading (holding weights) of the upper body in an erect posture is presented. The model assumes that the lumbar muscles balance the externally applied flexion and lateral bending moments. The concept of a 'loading plane' whose axes are the two bending moments is introduced. Any point in the plane can be viewed as a 'loading-point' describing a combination of bending moments that are applied to the body. The study of lumbar-muscle load sharing revealed loading conditions that required activation or deactivation of a particular muscle. The loading plane thus could be divided into regions of activity and inactivity for each muscle, separated by a 'switching curve.' The concept of 'switching curves' proved very useful for examining previously described physiologic assumptions on the loading conditions of particular muscle groups, and for grouping the 22 muscles described in the model into ten functional units. Electromyographic validation studies were conducted and showed a high degree of correlation between the model predictions and actual measurements for the contralateral (with respect to the load) muscles and to a lesser degree of correlation for the ipsilateral muscles.
Acute pancreatitis and reduction of H+ ion concentration in gastric secretions in experimental acute myocarditis produced by Indian red scorpion, Buthus tamulus, venom.
Crude venom (4 mg/kg) of scorpion (B. tamulus) was given in saline to anaesthetized dogs and rabbits. It produced a reduction in gastric H+ ion concentration in dogs with acute myocarditis. Simultaneously an increase in circulating amylase and lipase level was also observed. However 60% venom poisoned rabbits showed an elevated lipase level without a parallel increase in amylase. It is suggested that the venom acts directly on exocrine pancreas to cause acute pancreatitis.
Elevation of plasma angiotensin levels in dogs by Indian red scorpion (Buthus tamulus) venom & its reversal by administration of insulin+tolazoline.
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Disseminated intravascular coagulation & disturbances in carbohydrate & fat metabolism in acute myocarditis produced by scorpion (Buthus tamulus) venom.
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Polycyclic aromatic hydrocarbons in C8 isomer aromatic feed: analysis by GC, GC/MS, and GC/FTIR techniques.
Polycyclic aromatic hydrocarbons (PAHs), apart from their carcinogenic and mutagenic nature, create many problems in the petrochemical industry due to their tendency toward carbonization. Compounds in C8 aromatic isomer feed are analyzed by means of sample concentration, followed by separation of individual compounds by gas chromatography on a stainless steel OV-101 phase capillary column and identification by gas chromatography/mass spectrometry and gas chromatography/Fourier transform infrared spectroscopy. Various compounds belonging to different classes (mainly monocyclic, dicyclic, and tricyclic aromatics), oxygenated aromatics, and aliphatic saturates are quantified in the concentrated hydrocarbon residue of C8 isomer feed. Both unsubstituted and alkyl substituted ring type compounds are present. Concentrations obtained for PAH compounds in the C8 isomer feed range from 0.2 to 0.42 micrograms/mL.