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Biomedical subjects

S Krishna

Publications and source records attributed to S Krishna.

36 records · Page 2Linked to original sources
PubMed1989

Role of glutathione and dependent enzymes in anthracycline-resistant HL60/AR cells.

We studied the cellular enzymatic defenses against anthracycline-induced free radical damage in the HL60 human myelogenous leukemia cell line and in its anthracycline-resistant subline, HL60/AR. Intracellular glutathione (GSH) levels and gamma-glutamyl transpeptidase activity were lower in HL60/AR than in HL60 cells. Glutathione-S-transferase (GST) and glutathione peroxidase activities were similar in both cell lines. The intracellular distribution of GSH/GST was visualized by digitized video fluorescence microscopy, utilizing the fluorescent probe monochlorobimane fluorescence microscopy, utilizing the fluorescent probe monochlorobimane (MBCl), which is specifically conjugated to GSH by GST. In HL60 cells stained with the MBCl probe, a bright diffuse cytoplasmic and nuclear fluorescence pattern was observed, whereas in HL60/AR cells, the fluorescence was mostly localized to the Golgi apparatus with a lesser component of diffuse cytoplasmic and nuclear fluorescence. Pretreatment of HL60/AR cells with buthionine sulfoximine (BSO) partially reversed resistance to daunorubicin. This effect of BSO on resistance was associated not only with the abolition of localized MBCl fluorescence to the Golgi apparatus but also with increased intracellular accumulation and retention of daunorubicin. The results of our studies demonstrate that inhibition of GSH synthesis in HL60/AR cells results in significant sensitization to daunorubicin and suggest that changes in the intracellular distribution of GSH/GST and/or increased drug retention may be involved in mediating this effect.

Antibiotics, Antineoplastic↗
PubMed1989

Expression of glycoprotein D of herpes simplex virus type 1 in a recombinant baculovirus: protective responses and T cell recognition of the recombinant-infected cell extracts.

Recombinant baculoviruses expressing glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1) have been generated. The proteins expressed from the recombinants have been characterized using monoclonal antibodies on Western blots and by immunoprecipitation. Partially glycosylated 48K polypeptides have been identified as products of the gD gene. Polyclonal sera from H-2k mice infected with HSV-1 recognized the same polypeptides. Furthermore, draining lymph node cells from H-2k mice infected with HSV-1 proliferated in vitro in response to recombinant-infected cell extracts. Immunization with such extracts generated high titre complement-dependent and -independent neutralizing antibody and the mice were protected against a challenge with HSV-1.

Animals↗
PubMed1989

Regulated nocturnal hypothermia induced in pigeons by food deprivation.

The daily body temperature (Tb) cycle of pigeons is altered by food deprivation in that Tb falls to lower and lower levels on consecutive nights after the onset of deprivation, whereas the Tb levels during corresponding days remain nearly unchanged. Manipulations of spinal cord temperature, a major feedback parameter in the avian thermoregulatory system, reveal that episodes of nocturnal hypothermia are regulated. The spinal cord threshold temperature for inducing increases in metabolic heat production falls to progressively lower levels each night and returns to normal euthermic levels during the day.

Animals↗
PubMed1988

Cerebral anaerobic glycolysis and reduced cerebral oxygen transport in human cerebral malaria.

In 12 patients comatose with cerebral malaria, cerebral blood flow was 52.2 (SE 4.0) ml/100 g per min, within the reported range for healthy controls, but cerebral vascular resistance was raised at 1.66 (0.19) mm Hg/ml per 100 g per min. Cerebral oxygen consumption (1.90 [0.23] ml/100 g per min), and cerebral arteriovenous oxygen content difference (3.5 [0.43] ml/dl) were subnormal, while cerebral venous pO2 (5.7 [0.2] kpA) was raised. After recovery of consciousness there were significant decreases in arterial lactate concentration (2.44 [0.45] to 1.19 [0.45] mumol/l) and cerebral lactate production (17.4 [7.9] to 5.6 [1.1] mmol/100 g per minute). These results provide evidence of cerebral anaerobic glycolysis associated with inadequate oxygen delivery to the brain consistent with either inhibition of cerebral oxidative metabolism or the microcirculatory obstruction envisaged in the "mechanical" hypothesis for cerebral malaria.

Adolescent↗
PubMed1987

Influence of spinal and hypothalamic warming on metabolism and sleep in pigeons.

Animals were prepared with electrooculogram (EOG), cortical electroencephalogram (EEG), and electromyogram (EMG) electrodes and with spinal and/or hypothalamic thermodes. Experiments were run at a cold and a neutral ambient temperature (Ta) during the dark portion of a 24-h light-dark cycle. Metabolic rate, temperatures, EEG, EMG, and EOG were measured continuously for 4-h periods with hypothalamic or spinal temperature unmanipulated or warmed to the level measured during the light. The cold Ta increased metabolic rate over the neutral Ta, but did not influence total sleep time (TST) or rapid-eye-movement sleep (REM) as percent TST. At the cold Ta, spinal warming resulted in reduction in REM as a percent TST. Spinal warming frequently caused a fall in body temperature (Ta). A plot of REM as a percent TST vs. the fall in Tb, including data for all animals and all conditions, revealed a clear correlation between fall in Tb and reduction in REM. Hypothalamic warming had no influence on metabolic rate, Tb, or distributions of arousal states. Cold thermal stimuli caused by a fall in Tb can inhibit REM in birds as it can in mammals independently of thermoregulatory drive.

Animals↗
PubMed1987

Carbamazepine and carbamazepine-10,11-epoxide pharmacokinetics in an overdose patient.

A case report on a 13-year-old girl with idiopathic grand mal epilepsy who ingested 34 g carbamazepine (CBZ) and 80 mg clonazepam is presented. The patient survived but suffered severe temporary neurological toxicity characteristic of CBZ. CBZ was 79.6 +/- 2.8% bound to serum protein and carbamazepine-10,11-epoxide (CBZ-E) binding was essentially concentration dependent. CBZ and CBZ-E elimination half-lives were 26 and 16.5 h respectively. An inhibitory metabolic interaction with the co-ingested clonazepam is suggested.

Adolescent↗
PubMed1983

Severe hypoglycemia and hyperinsulinemia in falciparum malaria.

We studied the occurrence, clinical manifestations, and mechanism of hypoglycemia in patients with falciparum malaria in eastern Thailand. Hypoglycemia, which was often severe and recurrent, occurred in 17 patients, including 12 in a series of 151 patients with cerebral malaria. Thirty episodes were investigated. Plasma concentrations of insulin and C peptide were inappropriately high, and lactate and alanine concentrations were significantly higher than in patients with falciparum malaria who were normoglycemic (P less than 0.05). Sixteen patients had received quinine; plasma quinine and insulin concentrations were correlated at the time of hypoglycemia (P = 0.007). In seven healthy fasting volunteers intravenous quinine increased the mean plasma insulin concentration (+/- S.D.) from 8.9 +/- 3.1 to 17.1 +/- 8.4 mU per liter (P = 0.02) and reduced the mean plasma glucose concentration from 88 +/- 20 to 68 +/- 23 mg per deciliter (P = 0.002). Our observations indicate that in falciparum malaria quinine-induced insulin secretion may precipitate hypoglycemia, but other factors, including the large glucose requirements of the malaria parasites may also contribute. This important complication, associated with pregnancy and severe disease, must be excluded in all patients with falciparum malaria who have impaired or deteriorating consciousness.

3-Hydroxybutyric Acid↗
PubMed1983

Plasmodium yoelii: blood oxygen and brain function in the infected mouse.

The carriage of oxygen by the blood and the in vivo response of the brain were investigated in mice infected with a lethal strain of Plasmodium yoelii. All mice with parasitaemia exceeding 70% were severely anaemic (Hb 3.5 +/- 1.8 g/dl; mean +/- 1 SD), acidotic (blood pH 7.04 +/- 0.06) and hypoglycaemic (blood glucose 0.6 +/- 0.76 mumol/ml). The oxyhaemoglobin dissociation curve (ODC) of blood from heavily infected mice was shifted right as compared to controls, but the increase in p50 was less than expected from the accompanying acidosis. The reduced shift right was due to a decrease in the 2,3-DPG/Hb ratio in infected animals (0.72 +/- 0.12, n = 17 vs 1.10 +/- 0.09, n = 12 in controls). Despite the severity of terminal infection, the cerebral pH and the relative steady-state concentrations of PCr, ATP and Pi measured in vivo by nuclear magnetic resonance (31P NMR) were normal. Alterations in brain energy status and pH cannot account for cerebral signs or death in this proposed mouse model of cerebral malaria.

Adenosine Triphosphate↗
PubMed1983

Quinine disposition kinetics.

Intravenous quinine dihydrochloride (5 mg kg-1 over 5 min) was given to seven healthy male volunteers. There were minor subjective symptoms in all subjects but no significant changes in pulse or blood pressure. There was significant prolongation of the electrocardiographic QRS and rate corrected QT intervals which was greatest between 1 and 4 min after completion of the quinine infusion. Values then returned towards baseline. Plasma concentrations of quinine were measured spectrophotofluorimetrically after benzene extraction. Peak plasma concentrations (mean +/- 1 s.d.) after the infusion were 5.1 +/- 1.3 mg 1(-1). Pharmacokinetic analysis fitted a two compartment open model in each case; distribution half-time (t 1/2, lambda 1) was 1.89 +/- 0.54 min (mean +/- 1 s.d.), elimination half-time (t 1/2, z) 11.1 +/- 2.1 h, apparent volume of the central compartment (V1) 0.57 +/- 0.32 1 kg-1, total apparent volume of distribution 1.80 +/- 0.37 1 kg-1 and total clearance 1.92 +/- 0.45 ml min-1 kg-1.

Adolescent↗
PubMedDate not supplied

Management of severe malarial infection.

Severe malaria is a major cause of infant and childhood death in the tropics. Effective management relies on rapid diagnosis, prompt administration of parenteral schizonticidal antimalarial drugs, careful fluid balance, prevention of convulsions and early recognition of complications such as hypoglycemia, metabolic acidosis, anemia, pulmonary edema, renal failure, bleeding and supervening bacterial sepsis. The mortality of treated cerebral malaria remains 20%. New, more rapidly acting antimalarials and earlier referral of children with complicated infections should reduce this unacceptable death rate.

Acute Disease↗
PubMedDate not supplied

Treatment of malaria: some considerations and limitations of the current methods of assessment.

The currently used methods for assessing the therapeutic response to antimalarial drugs are relatively imprecise and insensitive. These methods are inadequate in severe malaria when the objectives of treatment are to save life and prevent complications. Very large studies are needed to demonstrate significant differences in mortality, but measurement of the rates of clinical, biochemical, and parasitological response may provide useful comparative information. Definitions, assessment criteria, procedures, and data collection forms should be standardized and evaluated prospectively. Antimalarial drug treatment in different clinical situations should be assessed in terms of the balance between the risks of drug toxicity and the benefits of the antimalarial drug action. This balance is considerably different in severe falciparum malaria compared with uncomplicated malaria infections.

Animals↗
PubMedDate not supplied

The pharmacokinetic properties of intramuscular quinine in Gambian children with severe falciparum malaria.

Plasma quinine concentrations were measured in 21 Gambian children with severe falciparum malaria after intramuscular administration of a 20 mg (salt) per kg loading dose of quinine dihydrochloride followed by 10 mg/kg at 12 h intervals. Quinine was well absorbed reaching mean peak concentrations of 15.6 (standard deviation [SD] 4.5) mg/litre in a median time of 3 h (range 1-6 h). A one compartment model was fitted to the plasma concentration-time profile. The mean estimated systemic clearance (Cl/F) was 0.89 (SD 0.81) ml/kg/min and the mean elimination half life was 18.8 (SD 8.0) h. Two patients, one of whom died, had low plasma quinine levels which remained below 10 mg/litre. Mean peak and trough plasma concentrations after subsequent intramuscular doses ranged between 11.1 and 15.1 mg/litre. In most cases this dose regimen provided a satisfactory profile of blood concentrations for the treatment of severe malaria in children.

Animals↗
PubMedDate not supplied

The pituitary-thyroid axis in severe falciparum malaria: evidence for depressed thyrotroph and thyroid gland function.

Abnormal thyroid function is strongly associated with mortality in severe non-thyroidal illness. We have assessed the pituitary-thyroid axis serially in 18 Thai adults with severe falciparum malaria and in 18 matched controls. The admission total serum thyroxine (T4) concentrations of the patients (median [range]: 64 nmol/litre [less than 30-91]) were significantly lower than those of controls (81 nmol/litre [61-133]; 2P less than 0.01), and remained depressed until after fever and parasite clearance. Two patients who died in hospital had admission serum T4 concentrations less than 35 nmol/litre. The admission basal serum thyrotropin (TSH) levels of the patients (0.9 mU/litre [less than 0.2-3.1]) were similar to those of controls (1.3 mU/litre [less than 0.2-3.7], 2P greater than 0.1) and remained normal throughout fever and parasitaemia. Thirty-minute TSH increments during a thyrotropin-releasing hormone test on admission were reduced in 13 patients with severe malaria (4.1 mU/litre [0.7-8.1]) relative to those in convalescence (7.1 mU/litre [1.7-14.4], n = 10, 2P less than 0.01) and controls (5.6 mU/litre [3.3-12.9], n = 9, 2P less than 0.05). These findings suggest that thyrotroph and thyroid gland function are depressed during acute, severe malaria. As these changes may be an adaptation to accelerated catabolism, the role of thyroid replacement in such patients is uncertain.

Adolescent↗
PubMedDate not supplied

Intracranial pressure in childhood cerebral malaria.

Lumbar punctures were performed in 40 Gambian children with acute cerebral malaria aged between 18 months and 10 years. The mean opening pressure was elevated in 32 (80%) of the children, but was not significantly different in the 14 fatal cases compared with survivors: 110 (standard deviation 71) versus 131 (58) mm of cerebrospinal fluid respectively. Cerebral perfusion pressures were also similar in the 2 groups: 64 (20) mm Hg versus 64 (11) mm Hg respectively. There was no clear clinical evidence of raised intracranial pressure, and no evidence of deterioration immediately following lumbar puncture. Nevertheless brain swelling, and consequent brain-stem compression, may contribute to a fatal outcome in cerebral malaria--particularly in those children who die from sudden respiratory arrest. A prospective evaluation of osmotic agents in childhood cerebral malaria seems to be justified.

Child↗