Quantitative Assessment of Muscle Activity and Joint Load in Braced and Unbraced Osteoarthritis Knee by External Strain Gauge Sensor.

Objectives: Altered biomechanics leads to the development of degenerative joint disease. The joint pressure and dynamic loading varies during activities of daily living. The study was undertaken to assess the muscle activation pattern of the medial and lateral knee compartments (tibiofemoral joint) during gait in osteoarthritis subjects without and with knee brace undergoing either exercise therapy or balance therapy. The joint load was assessed by the strain gauge transducer and the weight shift pattern is taken as an indicator for the muscle activation pattern. Methods: In a prospective design study on 57 male subjects diagnosed osteoarthritis knee with KellagrenLawrennce scale walked barefooted with and without designed offloader knee brace on a level surface for three minutes. The subjects were allocated in two different study groups i.e. Conventional (exercise therapy) (Control Group, n=31) and Structured Neuromuscular Postural Training (SNPT) group (Balance therapy) (Study Group, n=26). The subjects were sub grouped as pre-elderly (40-60 Years) and elderly (>61 years) group in both. The quantitative assessment of muscle activity and joint loading with and without knee brace was done using designed strain gauge sensor instrument. The pressure changes of strain gauges of muscles around the knee joint viz. vastus medialis (VM), vastus lateralis (VL), semi membranosus / tendinosus (Medial Hamstring) (MH), Biceps Femoris (Lateral Hamstring) (LH), gastro-soleus (GS) and tibialis anterior (TA) muscles during normal gait were observed at baseline and 6 weeks follow up after undergoing exercise therapy or balance therapy treatment as per allocation of study groups. The digital values from MATLAB were recorded and analyzed. Results: At the end of 6 weeks conventional / SNPT (structured neuromuscular postural training) treatments, medial hamstring muscle activity showed significant difference (p<0.001) in pre-elderly subgroup, while significant difference was seen in vastus laterals (VL), medial hamstring (MH) (p<0.005) and lateral hamstring (LH) muscles (p<0.001) in elderly subgroup

2-Deoxy-D-glucose reverses the Indian red scorpion venom-induced cardiopulmonary abnormalities in anesthetized rats.

Role of 2-Deoxy-D-glucose (2-DG) in reversing the Indian red scorpion (Mesobuthus tamulus concanesis Pocock, MBT) venom-induced toxicity was examined. Femoral arterial pressure, ECG and respiratory movements were recorded in urethane anesthetized rats. Plasma glucose and serum insulin levels were also estimated. Intravenous injection of 5 mg/kg MBT venom produced immediate decrease in mean arterial pressure, heart rate and respiratory frequency  followed by an increase and subsequent progressive decrease. ECG pattern exhibited ischaemic changes. There was hyperinsulinemia after venom without corresponding decrease in plasma glucose. The animals died within 37±9 min and demonstrated significant increase in pulmonary water content. 2-DG pretreatment (0.5 g/kg, iv) improved the cardiopulmonary abnormalities induced by venom and the animals survived for nearly 120 min. There was no hyperinsulinemia and increased pulmonary water content in these animals. In insulin (2 IU/kg) treated rats, the MBT venom-induced cardiopulmonary abnormalities were attenuated and ECG abnormalities were reversed. The pulmonary water content in these animals exhibited a decreasing trend and the animals survived for 120 min. Repaglinide (10 mg/kg, iv) pretreatment failed to reverse the venom-induced cardiopulmonary changes including the increased pulmonary water content. The survival time was similar to venom only group. The present results reveal that 2-DG reverses the venom-induced cardiopulmonary toxicity probably by restoring insulin sensitivity.

Opinion: Pathophysiological approach to the management of scorpion envenomation.

Indian red scorpion (Mesobuthus tamulus; MBT) produces lethal stings and is a matter of concern in certain parts of India. MBT envenomation produces multi-systemic involvement, thus presents difficulty in the management. Symptomatic treatment has been practiced earlier that failed to relieve the toxic effects of the venom. Therefore, present manuscript deals with pathophysiologically based approach in the management of toxicity considering the merits and the demerits of treatment protocols so as to evolve a consensus in the treatment strategies of scorpion envenomation.

2-Deoxy-D-glucose alters the cardio-respiratory parameters in anaesthetized rats.

2-Deoxy-D-Glucose (2-DG), a synthetic analogue of glucose, is used as an anticancer agent either alone or in combination with other tumor treatment protocols. The present study was conducted to identify the systemic effects of 2-DG on parameters of vital importance. The blood pressure, ECG and respiratory excursions were recorded in anesthetized adult rats. At the end (after 120 min) of experiments, the plasma glucose and serum insulin levels were estimated. Injection of 2-DG (0.5 g/kg) produced an immediate increase in mean arterial pressure (MAP) and respiratory rate. The increase in MAP continued throughout the period of observation (120 min) and the maximal increase was seen at 90 min (27%). Whereas, the respiratory rate decreased by 17% at 15 min which decreased further to 37% by 120 min. Heart rate also decreased after 2-DG in a timedependent manner and 40% decrease was observed at 120 min. Administration of 2-DG increased the plasma glucose level significantly (30%) as compared to saline control group but did not increase the serum insulin level. The results indicate that 2-DG alters the cardio-respiratory parameters by mechanisms unrelated to plasma insulin activity.

Effect of ischaemia & aglycaemia on the synaptic transmission in neonatal rat spinal cord in vitro.

BACKGROUND & OBJECTIVES: In vitro models of anoxia have revealed severe changes in neuronal functions after ischaemia but not after aglycaemia, although hypoglycaemia produced severe neuronal dysfunctions sometimes leading to coma. The present study was therefore undertaken to examine and compare the effects of aglycaemia with that of ischaemia on synaptic transmission in vitro. METHODS: Spinal cord from the neonatal rat was isolated, hemisected and placed in a chamber perfused with standard physiological solution. The stimulation of a dorsal root elicited monosynaptic (MSR) and polysynaptic (PSR) reflex potentials in the segmental ventral root. The effects of suprefusing glucose free medium (aglycaemia) and superfusing glucose free and O2 free medium (ischaemia) were examined on these reflexes. RESULTS: Superfusion of aglycaemic solution did not alter the magnitude of MSR or PSR in the first 15 min and subsequently there was a time-dependent depression of the reflexes (P < 0.05). The ischaemic solution depressed the reflexes in a time-dependent manner from the very beginning. The 50 per cent depression of the reflexes occurred around 25 and 15 min, for aglycaemia and ischaemia, respectively. In the presence of Mg2+, the aglycaemia-induced depression of MSR was completely blocked but the ischaemic response was attenuated partially as the reflex was abolished by 80 min. INTERPRETATION & CONCLUSION: The results of the present study indicate that the aglycaemia and ischaemia depressed the synaptic transmission to the same extent though there were differences in their onset and progress. Aglycaemia involves N-methyl-D-aspartate (NMDA) receptor-dependent (Mg2+ sensitive) mechanism, while ischaemia-induced depression involves other mechanisms in addition to NMDA.

Phenyldiguanide activates cardiac receptors to produce responses by involving three different efferent pathways in anaesthetized rats.

The present study was undertaken to determine the afferent and efferent pathways involved in the phenyldiguanide (PDG)-induced reflex response in rats. Intravenous (iv) injection of PDG (10 microg/kg), produced hypotension, bradycardia and apnea over a period of time. Bilateral vagotomy abolished the PDG-induced reflex changes. Atropine (2 mg/kg; iv) blocked only the bradycardiac response produced by PDG, while prazosin (0.5 mg/kg; iv) blocked the hypotensive response, and bilateral vagotomy in these animals abolished the apneic response. In separate series of experiments, intrapericardial injection of lignocaine abolished the hypotensive and bradycardiac responses evoked by PDG in artificially ventilated rats. The results reveal that the PDG-induced reflex is mediated through vagal afferents originating from the heart and efferents involve three different pathways. The bradycardiac response was through the muscarinic receptors, the hypotension is mediated through alpha1 adrenoceptors and the apnea presumably through the spinal motoneurones supplying the respiratory muscles.

Protective role of estrogen in the neurodegenerative disorders.

Estrogen is an anabolic hormone of gonadal cells and it also modulates the growth and differentiation of non-gonadal cells like neuron/glia and protects them against the injury. The anabolic or protective actions of estrogen on the neuronal cells are mediated by the modulation of intracellular factors such as insulin like growth factor (IGF-I), tyrosine kinase A (Trk A), nerve growth factors (NGF) etc. It also modulates the action of neurotrophins which in turn regulate the synaptogenesis, synaptic plasticity and synaptic functions. By these actions estrogen prevents or slows down the neurodegenerative process.

Indian red scorpion venom modulates spontaneous activity of rat right atria through the involvement of cholinergic and adrenergic systems.

The effect of Indian red scorpion (Mesobuthus tamulus concanesis, Pocock; MBT) venom was investigated on isolated rat right atrial preparations. MBT venom (0.001-3.0 micrograms/ml) exhibited a peculiar concentration-response pattern with respect to rate. The venom concentrations between 0.001-0.01 microgram/ml increased the atrial rate (phase I), followed by a relative decrease with 0.03-0.3 microgram/ml (phase II), and then an abrupt increase with 0.6-3.0 micrograms/ml (phase III). On the other hand, the force was unaltered by venom at phases I and II, while an increase was seen at phase III (3.0 micrograms/ml). Propranolol (0.1 microM) completely blocked the cardiostimulant action of venom at phase III. Further, this stimulant action of venom was absent in atria obtained from reserpinized animals. Pretreatment with atropine (0.3 microM), produced tachycardia at concentrations 0.1-0.3 microgram/ml of venom. But, hexamethonium (30 microM) had no influence on the venom (0.1 microgram/ml)-induced alterations in rate. However, MBT venom increased the acetylcholinesterase (AChE) activity (2-3 fold) in a concentration-dependent manner. Tetrodotoxin (2 microM), did not block the increase in rate produced by 0.01 microgram/ml of venom. Results suggest that, MBT venom-induced alterations of cardiac rhythmicity are mediated through cholinergic as well as adrenergic mechanisms depending upon the concentrations. The modulation of atrial rate at very low concentrations may be due to the direct action of venom on the atrium.

Indian red scorpion (Mesobuthus tamulus concanesis, Pocock) venom prolongs repolarization time and refractoriness of the compound action potential of frog sciatic nerve in vitro through calcium dependent mechanism.

Effects of Indian red scorpion (M. tamulus concanesis; MBT) venom on the compound action potential (CAP) of sciatic nerve in vitro were examined. MBT venom (0.1-6.0 micrograms/ml) prolonged the repolarization time and refractory period of the CAP in a concentration-dependent manner with maximal potentiation occurring at 6 micrograms/ml (about 100-200 times of the initial). At 1 microgram/ml of venom the prolongations were 40-50 times the initial durations and this concentration was used for subsequent experiments. Rise time, threshold, and conduction velocity of CAP were not altered by MBT venom (1 microgram/ml). In Ca(2+)-free medium, the venom-induced prolongations were only 2-6 times the initial response but addition of Ca2+ in the same medium then prolonged than by 50-70 times. The Ca2+ channel antagonists (nifedipine, 10 microM or Mg2+ ions, 5 mM) attenuated the venom (1 microgram/ml)-induced prolongation of repolarization time and refractory period. However, venom-induced prolongation of CAP responses were still significantly greater than the control in presence of these antagonists. The results indicate that MBT venom-induced increases in repolarization time and refractory period of the action potential greatly depend upon the presence of Ca2+ ions in the medium. The Ca2+ influx was through the L-type of Ca2+ channels.

Augmentation of phenyldiguanide-induced bradycardia by Buthus tamulus venom in adult rats.

Intravenous injection of phenyldiguanide (PDG) in anaesthetized rats produced dose-dependent (1-10 micrograms/kg) decrease in heart rate for a period of time (time-response area). The maximum response occurred at 10 micrograms/kg PDG. Administration of B. tamulus (BT) venom as low as 20 micrograms/kg augmented the PDG-induced bradycardia response by 2.5 times the initial PDG (10 micrograms/kg) response. The maximal augmentation was observed after 60 min of venom injection. Increasing the BT venom concentration to 40 micrograms/kg failed to enhance the reflex response (1.7 times the initial response). The threshold concentration of BT venom was 4 micrograms/kg. BT venom (100 micrograms/kg) alone, decreased the heart rate significantly only after 90 min. Results indicate that, even the sublethal concentrations of BT venom sensitize the reflexes elicited by PDG.

Effect of streptozotocin-induced diabetes on growth and proteolytic activity of different muscles in rats.

Fibre and non-fibre components and proteolytic activity of fore- and hindlimb muscles with different fibre composition and functions were examined in streptozotocin-induced diabetic rats. From hindlimb, extensor digitorum longus (EDL), medial gastrocnemius (MG) and soleus (SOL) were selected to represent muscles rich in fast oxidative-glycolytic, fast glycolytic and slow oxidative fibres, respectively. The biceps brachii (BB) and extensor carpi radialis longus (ECRL), represented forelimb muscles having similar fibre composition but performing flexor and extensor functions respectively. Among the five muscles studied, all but SOL showed decrease in muscle weight and protein in diabetic rats indicating the atrophy of these muscles. Atrophy was greater in EDL and MG as compared to ECRL and BB. This differential atrophy could be negatively correlated to the percentage of slow oxidative fibres. Despite the loss of fibre mass in diabetic group, elevated fibre protein concentration was observed in BB (flexor) but not in ECRL (extensor). There was a significant reduction in non-fibre protein concentration with markedly enhanced alkaline proteolytic activity in EDL of diabetic rats. Non-protein solid concentration was also increased in EDL and MG. These observations showed that fast muscles are more susceptible to diabetes induced atrophic changes and diabetes affected various muscle components differently in muscles with different fibre composition and functions. Therefore, fibre composition and function of a muscle may be the factors in determining muscle growth in diabetes.

Significance of monosynaptic and polysynaptic reflexes in neonatal rat spinal cord in vitro.

Stimulation of a dorsal root in an isolated spinal cord, elicited a monosynaptic reflex (MSR) in the corresponding ventral root at a latency of 3-5 msec and a dorsal root reflex (DRR) in an adjacent dorsal root 2-3 times the latency of MSR. The magnitude of DRR was 10 times smaller than the MSR. These reflexes could be decreased by the agents which suppress synaptic transmission e.g. either by decreasing the [Ca2+]0 or by increasing [Mg2+]0. In the absence of magnesium ([Mg2+]0) in the perfusing medium, the MSR was 15-20% greater in its magnitude and the segmental polysynaptic reflex (PSR) was distinctly seen at 8-10 msec latency. Segmental PSR disappeared when [Mg2+]0 ions are added to perfusing medium probably indicating the involvement of N-methyl-D-aspartate receptors. Further, in this preparation homosynaptic inhibition and pre- or post-synaptic inhibitions could be elicited. This preparation, thus serves as useful model for the study of central synaptic transmission to study the pharmacological or neurotoxic agents.

Thyrotropin releasing hormone-induced potentiation of spinal monosynaptic reflex in rats in vitro.

Superfusion of thyrotropin-releasing hormone (TRH) in neonatal rat spinal cord in vitro produced dose (0.01-1.00 microM) dependent potentiation of monosynaptic reflex (MSR) which was maximum (44% of control) at 1 microM of TRH. But no ventral root depolarization was observed with TRH (1 microM) although potassium concentration out side ([K+]0) when increased produced a depolarization at the magnitude of 0.2 mV/mM of [K+]0. TRH-induced potentiation of MSR was not altered in spinal cords, obtained from the animals pretreated with 5,7-dihydroxytryptamine or 6-hydroxydopamine. Neither serotonin antagonists (spiperone, ketanserin, cyproheptadine or 3-troponyl-indole-3-carboxylate) nor adrenergic antagonists (phentolamine or haloperidol) could attenuate TRH-induced potentiation. Inhibition of MSR observed in the spinal cord elicited by stimulating the adjacent dorsal root was unaffected by TRH. The results suggest that, TRH potentiates MSR by directly acting on the motoneurons, without involving presynaptic serotonergic or catecholaminergic neuronal systems or the disinhibition of pre- or post-synaptic inhibition in the spinal cord.

Study of primary convergence insufficiency.

The present study was done to find out the incidence of primary insufficiency of involuntary convergence and evaluate the relative efficacy of synoptophore treatment against home exercise in its management. During the period of study, 2162 cases in the age group 15 to 35 years were studied for convergence in detail. It was found out that the incidence of primary convergence insufficiency is quite high (7.7% of total orthoptic clinic attendance). It commonly affects those who are constantly engaged in near work. Response to synoptophore exercises and home exercises is comparably equal. Recurrence of the ailment after stopping the exercises is not uncommon.

Protein energy ratio as a critical factor in determining growth & glycogen content of muscles in rats.

Effect of protein deficiency, which was produced in rats either by feeding low protein diet (8% protein) ad libitum (PD) or by restricting the amount of diet containing 15 per cent protein (protein calorie deficiency; PCD) on the growth in terms of muscle weight, length, cross-sectional area, protein and glycogen content was studied in extensor digitorum longus (EDL), medial gastrocnemius (MG) and plantaris (PL) muscles in rat. Because of decreased total calorie intake, PCD group exhibited higher value for protein/total calorie consumption. Excepting glycogen concentration, the retardation of growth in terms of all parameters studied was less in the PCD group. Glycogen concentration (mg/g muscle weight) in the PCD group was 3.0 +/- 0.3 in EDL and 2.6 +/- 0.3 in PL, whereas the values in PD group were 1.0 +/- 0.1 in EDL and 1.1 +/- 0.2 in PL respectively. This glycogen sparing effect was not evident in MG of PCD group possibly due to the greater number of glycolytic fibres. It is suggested that lesser retardation of growth of muscles and glycogen sparing effect in PCD group, could be due to altered metabolic changes resulting in enhanced gluconeogenesis.

Fatigue and contractile responses of rat hindlimb muscles following excessive dexamethasone administration.

Muscle weight, protein content and contractile performance (tetanic tension, fatigue and recovery) of extensor digitorum longus and soleus were investigated in rat following systemic administration of Dexamethasone (DX), 5 mg/kg/day for ten days. These animals showed marked reduction in food intake during the course of DX treatment. As a control, a group of food restricted (FR) rats receiving equal amount of food consumed by the DX treated rats was also studied along with the saline control group, to differentiate the effect of DX on muscle from that of dietary deficiency. There was a greater degree of atrophy (reduced muscle mass and protein content) of extensor digitorum longus in DX treated rats as compared to that of the FR rats. In-situ isometric tetanic tension per gram of muscle and per unit weight of protein was similar in both the muscles in the DX treated and the FR rats. There was increased fatiguability with reduced post fatigue recovery in both the muscles of DX treated rats as compared to the FR rats. The results indicate that besides atrophy of fast twitch muscles, DX increases the fatiguability and decreases the postfatigue recovery in both fast and slow muscles.