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1.
Indian J Physiol Pharmacol ; 60(2): 145-154, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-29809372

RESUMO

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 Kellagren-Lawrennce 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. Further, the muscle co-contraction has been higher for vastus medialis-medial hamstring (VM-MH) pair compared to vastus lateralis-lateral hamstring (VL-LH) pair without brace at baseline. The application of offloader valgus knee brace significantly increases VL-LH co-contractions in magnitude and decreases in VM-MH co-contractions at 6 weeks follow up. CONCLUSION: Muscle activity increased in medial hamstring both in pre-elderly and elderly subjects. While, Vastus Laterals and lateral hamstring showed increased activities in elderly subjects. Hence, balance training and the application of off loader knee brace will be helpful to redistribute the load on medial tibiofemoral compartment.


Assuntos
Braquetes , Articulação do Joelho/fisiologia , Atividade Motora/fisiologia , Músculo Esquelético/fisiologia , Osteoartrite do Joelho/fisiopatologia , Atividades Cotidianas , Adulto , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular/fisiologia , Osteoartrite do Joelho/terapia , Resultado do Tratamento
2.
Neuroscience ; 289: 349-57, 2015 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-25595991

RESUMO

Bisphenol A (BPA), a toxic chemical from plastics, is known to produce locomotor abnormalities which may imply the alteration in synaptic activity at Ia-α motoneuron synapse also. However the effect of BPA on this synapse is not known. Therefore, this study was undertaken to examine the effect of BPA on reflexes originating at Ia-α motoneuron synapse in the spinal cord. The experiments were performed on isolated hemisected spinal cords from 4 to 6d rats. Stimulation of a dorsal root evoked segmental monosynaptic (MSR) and polysynaptic (PSR) reflex potentials in the corresponding ventral root. Nitrite content (indicator of NO activity) of cords was estimated in the presence of BPA with/without antagonists. Superfusion of BPA (3-100µM) depressed the reflexes in a concentration- and time-dependent manner. The depression was ∼20, ∼50 and ∼70% at 10, 30 and 100µM of BPA, respectively. The 50% depression occurred around 15min at 30µM of BPA. Pretreatment with estrogen receptor (ERα) antagonist, tamoxifen, blocked the BPA-induced depression of reflexes, whereas, 17ß-estradiol, ER agonist, did not depress the reflexes even up to 10µM. Further, pretreatment with Nω-Nitro-l-arginine methyl ester hydrochloride (l-NAME) or hemoglobin (Hb) blocked the BPA-induced depression of spinal reflexes. Nitric oxide (NO) donor sodium-nitroprusside depressed the MSR and PSR in a concentration-dependent manner. The nitrite concentration of the cords exposed to BPA was 733µM/gm of tissue (three times the saline group). Pretreatment with tamoxifen/l-NAME/Hb blocked the BPA-induced increase of nitrite levels. The present observations indicate that BPA depressed spinal synaptic transmission through ERα-dependent NO-mediated mechanisms. The altered synaptic activity may implicate for neurobehavioral locomotor abnormalities after exposure to BPA.


Assuntos
Compostos Benzidrílicos/toxicidade , Receptor alfa de Estrogênio/metabolismo , Óxido Nítrico/metabolismo , Fenóis/toxicidade , Reflexo/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Inibidores Enzimáticos/farmacologia , Estradiol/farmacologia , Antagonistas de Estrogênios/farmacologia , Receptor alfa de Estrogênio/agonistas , Receptor alfa de Estrogênio/antagonistas & inibidores , Estrogênios/farmacologia , Etanol/farmacologia , Hemoglobinas/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Doadores de Óxido Nítrico/farmacologia , Nitritos/metabolismo , Nitroprussiato/farmacologia , Ratos , Reflexo/fisiologia , Solventes/farmacologia , Medula Espinal/crescimento & desenvolvimento , Medula Espinal/fisiologia , Raízes Nervosas Espinhais/efeitos dos fármacos , Raízes Nervosas Espinhais/crescimento & desenvolvimento , Raízes Nervosas Espinhais/fisiologia , Tamoxifeno/farmacologia , Técnicas de Cultura de Tecidos
3.
Indian J Exp Biol ; 49(1): 16-23, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21365991

RESUMO

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 microg/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.


Assuntos
Anestesia , Anormalidades Cardiovasculares/complicações , Anormalidades Cardiovasculares/tratamento farmacológico , Desoxiglucose/uso terapêutico , Pneumopatias/complicações , Pneumopatias/tratamento farmacológico , Venenos de Escorpião/toxicidade , Animais , Glicemia/efeitos dos fármacos , Carbamatos/farmacologia , Carbamatos/uso terapêutico , Anormalidades Cardiovasculares/induzido quimicamente , Anormalidades Cardiovasculares/fisiopatologia , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Índia , Insulina/sangue , Insulina/farmacologia , Insulina/uso terapêutico , Pneumopatias/induzido quimicamente , Pneumopatias/fisiopatologia , Isquemia Miocárdica/induzido quimicamente , Isquemia Miocárdica/complicações , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/tratamento farmacológico , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/complicações , Edema Pulmonar/tratamento farmacológico , Edema Pulmonar/fisiopatologia , Ratos , Respiração/efeitos dos fármacos , Venenos de Escorpião/antagonistas & inibidores , Ultrassonografia
5.
Acta Physiol (Oxf) ; 200(1): 87-95, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20331538

RESUMO

AIM: Stimulation of pulmonary C fibre receptors by phenylbiguanide (PBG, 5-HT(3) agonist) produces hypotension, bradycardia and tachypnoea or apnoea. However, tachypnoeic or apnoeic responses are not consistent. Therefore, this study was undertaken to delineate the actions of PBG on respiration and compared with those evoked by capsaicin (TRPV1 agonist). METHODS: Blood pressure, respiratory excursions and ECG were recorded in urethane anaesthetized adult rats. The effect of PBG or capsaicin was evaluated before and after ondansetron (5-HT(3) antagonist), capsazepine (TRPV1 antagonist) or bilateral vagotomy. In addition, their effect on vagal afferent activity was also evaluated. RESULTS: Bolus injection of PBG produced concentration-dependent (0.1-100 microg kg(-1)) hypotensive and bradycardiac responses, while there was tachypnoea at lower concentrations (0.1-3 microg kg(-1)) and apnoea at higher concentrations (10-100 microg kg(-1)). After vagotomy or after exposure to ondansetron both tachypnoeic and apnoeic responses were abolished along with cardiovascular responses. However, capsazepine (3 mg kg(-1)) did not block the PBG-induced reflex responses. Capsaicin (0.1-10 microg kg(-1)), on the other hand, produced a concentration-dependent apnoea, hypotension and bradycardia but tachypnoea was not observed. Ondansetron failed to block the capsaicin-induced reflex response while bilateral vagotomy abolished bradycardiac and hypotensive responses and attenuated the apnoeic response. In another series, vagal afferent activity and cardio-respiratory changes evoked by PBG were blocked by ondansetron. However, capsaicin failed to activate the PBG-sensitive vagal afferents even though cardio-respiratory alterations were observed. CONCLUSIONS: The present observations indicate that PBG produced tachypnoea at a lower concentration and apnoea at a higher concentration involving vagal afferents which are different from those excited by capsaicin.


Assuntos
Biguanidas/farmacologia , Capsaicina/farmacologia , Sistema Cardiovascular/inervação , Pulmão/inervação , Reflexo/efeitos dos fármacos , Fármacos do Sistema Sensorial/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Nervo Vago/efeitos dos fármacos , Vias Aferentes/efeitos dos fármacos , Vias Aferentes/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Frequência Cardíaca/efeitos dos fármacos , Fibras Nervosas Amielínicas/efeitos dos fármacos , Fibras Nervosas Amielínicas/fisiologia , Ratos , Mecânica Respiratória/efeitos dos fármacos , Agonistas do Receptor 5-HT3 de Serotonina , Antagonistas do Receptor 5-HT3 de Serotonina , Antagonistas da Serotonina/farmacologia , Canais de Cátion TRPV/agonistas , Canais de Cátion TRPV/antagonistas & inibidores , Vagotomia , Nervo Vago/fisiologia , Nervo Vago/cirurgia
6.
Acta Physiol (Oxf) ; 196(4): 365-73, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19133874

RESUMO

AIM: This study was performed to delineate the kinin (receptor)-dependent pathways in the Indian red scorpion (Mesobuthus tamulus; MBT) venom-induced pulmonary oedema as well as the augmentation of cardio-pulmonary reflexes evoked by phenyldiguanide (PDG). METHODS: In urethane-anaesthetized adult rats, the effect of venom on the PDG reflex responses (blood pressure, heart rate and respiration rate) and the pulmonary water content was ascertained using various antagonists(des- Arg, B(1) receptor antagonist; Hoe 140, B(2) receptor antagonist; N(omega)-nitro-l-arginine methyl ester (l-NAME), nitric oxide (NO) synthase inhibitor; methylene blue, soluble guanylate cyclase inhibitor; and glibenclamide, K(+)(ATP) channel blocker). The effect of phosphodiesterase V inhibitor (sildenafil citrate) on the reflex response and the pulmonary water content was also examined and compared with venom-induced responses. RESULTS: Intravenous injection of PDG (10 microg kg(-1)) evoked apnoea, bradycardia and hypotension lasting >60 s. Exposure to MBT venom (100 microg kg(-1)) for 30 min augmented the PDG reflex responses by two times and increased the pulmonary water content, significantly. Hoe 140 blocked the venom-induced responses (augmentation of PDG reflex and increased pulmonary water content) whereas des-Arg did not. l-NAME, methylene blue or glibenclamide also blocked the venom-induced responses. Furthermore, sildenafil citrate (that increases cGMP levels) produced augmentation of PDG reflex response and increased the pulmonary water content as seen with venom. CONCLUSION: The results indicate that venom-induced responses involve B(2) kinin receptors via the NO-dependent guanylate cyclase-cGMP pathway involving K(+)(ATP) channels.


Assuntos
Guanosina Monofosfato/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Óxido Nítrico/metabolismo , Edema Pulmonar/metabolismo , Receptor B2 da Bradicinina/metabolismo , Reflexo/efeitos dos fármacos , Venenos de Escorpião/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Biguanidas/administração & dosagem , Biguanidas/metabolismo , Bradicinina/análogos & derivados , Bradicinina/farmacologia , Antagonistas de Receptor B2 da Bradicinina , Inibidores Enzimáticos/farmacologia , Glibureto/farmacologia , Coração/efeitos dos fármacos , Coração/fisiologia , Hipoglicemiantes/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/fisiologia , Masculino , Azul de Metileno/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Piperazinas/farmacologia , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/fisiopatologia , Purinas/farmacologia , Ratos , Escorpiões , Agonistas do Receptor de Serotonina/administração & dosagem , Agonistas do Receptor de Serotonina/metabolismo , Citrato de Sildenafila , Sulfonas/farmacologia
7.
Indian J Pharmacol ; 41(6): 255-7, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20407555

RESUMO

AIM: Gastric dysfunctions are commonly seen after scorpion envenomation, and the underlying mechanisms are not clear. Therefore, the present study was undertaken to investigate the effect of Indian red scorpion (Mesobuthus tamulus, MBT) venom on gastric fundus muscle contraction and the underlying mechanisms involved. MATERIALS AND METHODS: In vitro isometric contraction was recorded from gastric fundus muscle strips on a chart recorder. The tissue was exposed to different concentrations of serotonin or crude MBT venom. The contractile responses to venom were expressed as the percentage of maximum contraction produced by serotonin at the beginning of each experiment. The contractile responses to 1.0 mug/ml of crude MBT venom were ascertained in the absence or presence of serotonin antagonist, methysergide. RESULTS: Serotonin produced concentration-dependent fundus contractions (0.004-4.0 muM), and maximum contractile response was observed at 4.0 muM of serotonin. Hence, the contractile response obtained at 4.0 muM of serotonin was taken for normalization. The crude MBT venom (0.1-1.0 mug/ml) produced a concentration-dependent increase in fundus contractions (as % of maximum fundus contraction produced by serotonin at 4.0 muM). The maximum response was observed at 1.0 mug/ml of crude venom and a further increase in the concentration, up to 3.0 mug/ml, did not increase the response. In a separate series of experiments, pre-treatment with methysergide (1.0 muM) significantly attenuated the contractile response elicited by the venom (1.0 mug/ml) (P<0.05) and blocked the serotonin (4.0 muM) response. CONCLUSION: The results suggest that the crude MBT venom produces gastric fundus contractions by partially involving serotonin.

8.
Indian J Physiol Pharmacol ; 52(3): 243-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19552054

RESUMO

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 time-dependent 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.


Assuntos
Antineoplásicos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Desoxiglucose/farmacologia , Eletrocardiografia/efeitos dos fármacos , Respiração/efeitos dos fármacos , Animais , Glicemia/efeitos dos fármacos , Insulina/sangue , Masculino , Ratos , Ratos Endogâmicos
9.
Indian J Physiol Pharmacol ; 52(3): 311-4, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19552066

RESUMO

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.


Assuntos
Antivenenos/imunologia , Antivenenos/uso terapêutico , Mordeduras e Picadas/tratamento farmacológico , Mordeduras e Picadas/fisiopatologia , Venenos de Escorpião/efeitos adversos , Animais , Mordeduras e Picadas/imunologia , Protocolos Clínicos , Humanos , Toxinas Biológicas/isolamento & purificação
11.
Toxicon ; 45(6): 735-43, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15804522

RESUMO

The experiments were conducted to identify the toxin that produces pulmonary oedema in Mesobuthus tamulus (BT) envenomed animals. Crude BT venom was subjected to Sephadex gel filtration (G-75) and the fractions were screened for optical density (OD), neurotoxicity (prolongation of compound action potential in frog sciatic nerve) and lethality. All these parameters exhibited a peak between 54-94 ml eluates. Fractions of this peak were pooled (SP) and loaded on to carboxymethyl cellulose column. The column was then eluted with increasing buffer concentrations at constant pH and temperature. Eluates were screened for neurotoxicity and OD. Four peaks of neurotoxic activity (T1-T4) were detected. T2 and T3 were lethal whereas T1 and T4 were non-lethal. T2 exhibited mainly neurotoxicity and failed to augment phenyldiguanide (PDG)-induced reflex response or to produce pulmonary oedema. T3 was having minimal neurotoxic actions but augmented PDG-reflex and produced pulmonary oedema. The effects of T3 persisted even after dialysis with 8 kDa cut-off filter but not those of T2. The T3 effects resembled toxic manifestations of BT venom and were blocked by aprotinin pre-treatment. T3 demonstrated a band at approximately 100 kDa in SDS-PAGE. The results demonstrate the presence of a lethal, high molecular weight, pulmonary oedema producing toxin in BT venom.


Assuntos
Edema Pulmonar/metabolismo , Venenos de Escorpião/toxicidade , Escorpiões/química , Toxinas Biológicas/toxicidade , Análise de Variância , Animais , Anuros , Aprotinina , Pressão Sanguínea/efeitos dos fármacos , Cromatografia em Gel , Cromatografia por Troca Iônica , Densitometria , Eletroforese em Gel de Poliacrilamida , Frequência Cardíaca/efeitos dos fármacos , Dose Letal Mediana , Edema Pulmonar/induzido quimicamente , Ratos , Reflexo/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Toxinas Biológicas/isolamento & purificação , Toxinas Biológicas/metabolismo
12.
Toxicol Lett ; 145(3): 231-7, 2003 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-14580894

RESUMO

The involvement of frequency-dependent depression (FDD) of synaptic transmission for the depressant action of the Ptychodiscus brevis toxin (PbTx) was investigated in neonatal rat spinal cord in vitro. The stimulation of a dorsal root by train of pulses (five stimuli) at different frequencies evoked potentials in the ventral root (monosynaptic reflex, MSR). Amplitude of the fifth response as percent of first response at 0.1, 0.2, 0.5, 1.0 and 2.0 Hz were 90, 80, 75, 70 and 50%, respectively. In Mg2+-free medium, PbTx depressed the MSR and also enhanced the FDD in a concentration-dependent manner. Further, the PbTx-induced depression can well be correlated with the enhancement of FDD (r=0.98). In the presence of Mg2+ (1.3 mM), the FDD was greater than that in the absence of Mg2+. But in the presence of Mg2+ PbTx did not alter FDD, even though there was 25% depression at 28 microM (significantly lesser than in Mg2+-free medium). The results indicate that the Mg2+-sensitive component of PbTx-induced depression of MSR is mediated via the neuronal systems involving FDD.


Assuntos
Ciclopentanos/farmacologia , Compostos Organofosforados/farmacologia , Reflexo Monosináptico/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Depressão Química , Estimulação Elétrica , Técnicas In Vitro , Magnésio/farmacologia , Ratos , Ratos Endogâmicos , Raízes Nervosas Espinhais/efeitos dos fármacos
13.
Indian J Med Res ; 118: 172-7, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14700352

RESUMO

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.


Assuntos
Glicina/farmacologia , Isquemia , Medula Espinal/patologia , Transmissão Sináptica , Animais , Animais Recém-Nascidos , Hipóxia Celular/fisiologia , Glucose/metabolismo , Hipóxia , Magnésio/metabolismo , Magnésio/farmacologia , N-Metilaspartato/metabolismo , Oxigênio/metabolismo , Perfusão , Ratos , Raízes Nervosas Espinhais/patologia , Sinapses , Fatores de Tempo
14.
Neuroscience ; 115(4): 1189-97, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12453490

RESUMO

The effects of Ptychodiscus brevis toxin (PbTx) on the Ia-alpha motoneuron synaptic transmission in neonatal rat spinal cord in vitro was examined. The stimulation of a dorsal root evoked monosynaptic (MSR) and polysynaptic reflex (PSR) potentials in the segmental ventral root in Mg2+-free medium. Superfusion with PbTx (2.8-84 microM) depressed the MSR and the PSR in a concentration-dependent manner. At 2.8 microM of PbTx, the depression of MSR and PSR was 24+/-8.3% and 37+/-9.7%, respectively. The maximal depression was seen at 84 microM of the toxin (78% for MSR and 96% for PSR). The concentration of toxin required to produce 50% depression was 28.3+/-6.4 microM for MSR and 5.5+/-1.1 microM for PSR. The PbTx (28 microM) did not alter the magnitude of the dorsal root or the ventral root potentials. Addition of MgSO4 (1.3 mM) or DL-2-amino-5-phosphonovaleric acid (APV; 10 microM) to the physiological solution abolished the PSR totally and decreased the MSR by about 30%. In both the conditions, the PbTx-induced depression of the MSR was attenuated significantly. The PbTx-induced depression was blocked completely in the presence of APV+6-cyano-7-nitroquinoxaline-2,3-dione (0.1 microM). NMDA (1 microM) by itself did not alter the magnitude of MSR or PSR but enhanced the PbTx-induced depression (28 microM) of PSR significantly. 7-Chlorokynurenic acid (3 microM; glycine(B) antagonist) did not block the PbTx-induced depression of MSR. D-serine (glycine(B) agonist) did not reverse the PbTx-induced depression of reflexes although it reversed the 7-chlorokynurenic acid-induced depression of PSR. The results indicate that the PbTx depressed the spinal reflexes without altering the magnitude of dorsal root or ventral root activity. The depression of the PSR involved NMDA receptors while that of the MSR involved NMDA and non-NMDA receptors. The PbTx actions did not involve the glycine(B) site of the NMDA receptor.


Assuntos
Células do Corno Anterior/efeitos dos fármacos , Toxinas Marinhas/farmacologia , Inibição Neural/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Reflexo de Estiramento/efeitos dos fármacos , Raízes Nervosas Espinhais/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Vias Aferentes/efeitos dos fármacos , Vias Aferentes/fisiologia , Animais , Animais Recém-Nascidos , Células do Corno Anterior/citologia , Células do Corno Anterior/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Interações Medicamentosas/fisiologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Magnésio/farmacologia , Masculino , Fusos Musculares/fisiologia , Inibição Neural/fisiologia , Oxocinas , Ratos , Ratos Endogâmicos , Receptores de N-Metil-D-Aspartato/fisiologia , Reflexo de Estiramento/fisiologia , Serina/farmacologia , Raízes Nervosas Espinhais/fisiologia , Sinapses/fisiologia , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia
15.
Toxicol Lett ; 128(1-3): 177-83, 2002 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-11869828

RESUMO

Effects of Ptychodiscus brevis toxin (PbTx) analogs on the spinal synaptic transmission in neonatal rats in vitro were evaluated. PbTx1/PbTx2 had aromatic groups and PbTx3/PbTx4 had aliphatic groups. All the analogs depressed monosynaptic reflex (MSR) and polysynaptic reflex (PSR) in a concentration-dependent manner. The maximal depression of MSR (75% from initial) and PSR (96%) was at 84 microM for PbTx1. Concentration to produce 25% inhibition from initial (IC25) by PbTx1 for MSR and PSR was < or =2.8 microM. The maximal depression of MSR (80%) was at 96 microM and PSR (100%) was at 32 microM by PbTx2. IC25 for MSR and PSR were 5.5 microM and <3.2 microM, respectively. PbTx3 decreased MSR by 25% maximally (=IC25) at 36 microM. The depression of PSR fluctuated and was maximal (75%) at 108 microM and IC25 was 6.2 microM. PbTx4 depressed MSR and PSR at the maximum of 35% at 32 microM and IC25 for MSR was 8.3 microM and for PSR was 35 microM. Rank order of potency of toxins for depressing MSR was PbTx1>PbTx2>>PbTx4>PbTx3; and for PSR it was PbTx2>PbTx1>PbTx3>>PbTx4. Results indicate that the toxins having aromatic groups exhibited greater neurotoxicity.


Assuntos
Toxinas Marinhas/toxicidade , Medula Espinal/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Depressão Química , Dinoflagellida/química , Dinoflagellida/metabolismo , Feminino , Técnicas In Vitro , Masculino , Oxocinas , Ratos , Medula Espinal/fisiologia
16.
Indian J Physiol Pharmacol ; 44(1): 43-9, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10919094

RESUMO

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.


Assuntos
Estrogênios/uso terapêutico , Doenças Neurodegenerativas/prevenção & controle , Estrogênios/fisiologia , Humanos , Receptores de Estrogênio/efeitos dos fármacos
18.
Indian J Exp Biol ; 38(9): 881-6, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12561945

RESUMO

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.


Assuntos
Biguanidas/farmacologia , Coração/efeitos dos fármacos , Receptores Adrenérgicos alfa 1/metabolismo , Receptores Muscarínicos/metabolismo , Reflexo/efeitos dos fármacos , Agonistas do Receptor de Serotonina/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Anestésicos Locais , Animais , Apneia/induzido quimicamente , Pressão Sanguínea/efeitos dos fármacos , Bradicardia/induzido quimicamente , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hipotensão/induzido quimicamente , Injeções , Lidocaína/farmacologia , Masculino , Neurônios Motores/metabolismo , Antagonistas Muscarínicos/farmacologia , Terminações Nervosas/efeitos dos fármacos , Ratos , Vagotomia
19.
J Physiol ; 521 Pt 2: 537-44, 1999 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-10581322

RESUMO

1. The involvement of pulmonary oedema produced by scorpion venom in augmenting a phenyldiguanide (PDG)-induced reflex response was evaluated in urethane-anaesthetized rats. 2. PDG-induced bradycardiac, hypotensive and apnoeic responses, expressed as time-response area, exhibited similarities before or after venom treatment. Hence, the time-response area of bradycardia was taken as a reflex parameter. Pulmonary oedema was determined by physical evaporation and histological methods. 3. Exposure to Indian red scorpion (Buthus tamulus, BT; i.v.) venom for 30 min increased the pulmonary water content (P < 0.05; Student's t test) and augmented the PDG-induced bradycardiac reflex response by more than 2 times (P < 0.001). The increase of pulmonary water content was maximal with 100 microg kg-1 of venom and the augmentation was maximal with 10 microg kg-1. In a separate series of experiments, the venom (100 microg kg-1)-induced pulmonary oedema was confirmed by histological and physical methods. In this group also, the venom augmented the reflex to the same magnitude. 4. Pulmonary oedema (physical and histological) and augmentation of the bradycardiac reflex response after BT venom (100 microg kg-1; i.v.) were absent in animals pretreated with aprotinin, a kallikrein-kinin inhibitor (6000 KIU; i. v.). 5. Ondansetron (10 microg kg-1; i.v.), a 5-HT3 receptor antagonist, failed to block the venom-induced pulmonary oedema (physical and histological) but blocked the venom-induced augmentation of the reflex. 6. The results of this study indicate that the venom-induced augmentation of the PDG reflex is associated with pulmonary oedema involving kinins utilizing 5-HT3 receptors.


Assuntos
Biguanidas/farmacologia , Edema Pulmonar/fisiopatologia , Reflexo/efeitos dos fármacos , Venenos de Escorpião/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Anestésicos Intravenosos , Animais , Apneia/induzido quimicamente , Apneia/fisiopatologia , Aprotinina/farmacologia , Bradicardia/induzido quimicamente , Bradicardia/fisiopatologia , Sinergismo Farmacológico , Feminino , Hipotensão/induzido quimicamente , Hipotensão/fisiopatologia , Masculino , Ondansetron/farmacologia , Tamanho do Órgão , Edema Pulmonar/induzido quimicamente , Ratos , Ratos Endogâmicos , Inibidores de Serina Proteinase/farmacologia , Antagonistas da Serotonina/farmacologia , Uretana , Água/análise
20.
Toxicon ; 37(12): 1697-709, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10519648

RESUMO

The present study was undertaken to identify 5-HT receptor subtypes involved in Buthus tamulus (BT) venom-induced augmentation of cardiac reflexes elicited by phenyldiguanide (PDG). Intravenous injection of PDG (10 microg/kg) produced parallel decrease in mean arterial pressure (MAP) and heart rate (HR) in urethane anaesthetized rats (r=0.82; p < 0.001). Injection of PDG (1-40 microg/kg, i.v.) produced concentration-dependent decrease in time-response area of the HR. After BT venom (20 microg/kg) the concentration-response curve was shifted to the left. Further, fall of MAP and HR in response to submaximal concentration of PDG (10 microg/kg) were augmented significantly. Pretreatment with 5-HT3 receptor antagonist (ondansetron; 10 microg/kg) intravenously, blocked the BT venom-induced augmentation of PDG reflex but spiperone (100 microg/kg; 5-HT1A/5-HT2 antagonist) or ketanserin (300 microg/kg; 5-HT2 antagonist) failed to do so. Afferent discharges elicited by PDG (10 microg/kg) in vagus nerve were doubled after exposure to BT venom. Ondansetron (100 microg/kg, i.v.) totally abolished the discharges after exposure to BT venom but not by spiperone or ketanserin. Intracerebroventricular injection of spiperone (100 microg/kg) but not ketanserin or ondansetron, blocked the BT venom-induced augmentation of PDG reflex. Results show that the BT venom-induced augmentation of reflex elicited by PDG is mediated through the involvement of 5-HT3 receptors peripherally and 5-HT1A type of receptors centrally.


Assuntos
Coração/efeitos dos fármacos , Receptores de Serotonina/metabolismo , Reflexo/fisiologia , Venenos de Escorpião/farmacologia , Nervo Vago/fisiologia , Animais , Biguanidas/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Coração/inervação , Frequência Cardíaca/efeitos dos fármacos , Injeções Intravenosas , Ketanserina/farmacologia , Ondansetron/farmacologia , Sistema Nervoso Periférico/metabolismo , Ratos , Receptores 5-HT1 de Serotonina , Receptores 5-HT3 de Serotonina , Escorpiões , Agonistas do Receptor de Serotonina/farmacologia , Espiperona/administração & dosagem , Espiperona/farmacologia
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