Search PubMed⌕ Search

Biomedical subjects

S Lahiri

Publications and source records attributed to S Lahiri.

At least 37 records · Page 2Linked to original sources
PubMed2001

Regulation of oxygen sensing in peripheral arterial chemoreceptors.

The carotid bodies are a small pair of highly vascularized and well perfused organs located at each carotid artery bifurcation, strategically situated to sense oxygen in arterial blood as it leaves the heart. Carotid body glomus cells are identified as the primary oxygen sensors, which respond to changes in blood P(O(2)) within milliseconds. Acute hypoxia causes a rapid increase in carotid sinus nerve (CSN) activity, providing afferent signals to the respiratory center in the brainstem. Glomus cells secrete numerous neurotransmitters that modulate CSN firing rates. This review will discuss major hypotheses that have emerged regarding acute oxygen sensing by glomus cells. In contrast, chronic responses to hypoxia are much slower, involving cytosolic reactions that take place over several minutes and nuclear reactions which occur over several hours. Converging concepts from different areas of research in oxygen sensing cells and tissues (including the carotid body) have been combined to describe molecular and biochemical changes that take place in the carotid body with chronic hypoxia. These include oxygen dependent proteolytic processes in the cytosol and gene transcription in the nucleus. In addition, cellular and nuclear responses to chronic hypoxia will be discussed.

Animals↗
PubMed2001

Randomized placebo-controlled trial of 2,3-dimercapto-1-propanesulfonate (DMPS) in therapy of chronic arsenicosis due to drinking arsenic-contaminated water.

BACKGROUND: Chronic arsenic toxicity, producing various clinical manifestations, is currently epidemic in West Bengal, India, Bangladesh, and other regions of the world. 2,3-Dimercapto-1-propanesulfonate, a chelating agent, increases excretion of arsenic in urine to several times the prechelation concentration but the therapeutic efficacy of 2,3-dimercapto-1-propanesulfonate in the management of chronic arsenic toxicity has been incompletely evaluated. We investigated the clinical use of 2,3-dmercapto-1-propanesulfonate in such patients. METHODS: Twenty-one consecutive patients with chronic arsenicosis were individually randomized into 2 groups: 11 patients (9 males and 2 females, age 30.63+/-11.4 years) received 2,3-dimercapto-1-propanesulfonate 100-mg capsules 4 times a day for 1 week and repeated in the 3rd, 5th, and 7th week with no drug during the intervening period. The other 10 patients (5 males and 5 females, age 34.4+/-14.41 years) were given placebo capsules (resembling 2,3-dimercapto-1-propanesulfonate) in the same schedule. The consumption of arsenic-contaminated water was terminated by all 21 subjects. Initial and posttreatment urinary arsenic excretion was determined in all cases. Sequential excretion of urinary arsenic was determined during the treatment of 2 drug- and 1 placebo-treated cases. The clinical features were evaluated by an objective scoring system before and after treatment. Routine investigation including liver function test and skin biopsy were also done before and after the treatment. Drug-associated toxicity was tabulated. RESULTS: Therapy with 2,3-dimercapto-1-propanesulfonate caused significant improvement in the clinical condition of chronic arsenicosis patients as evidenced by significant reduction of total clinical scores from 8.90+/-2.84 to 3.27+/-1.73; p < 0.0001. Exposure cessation alone with placebo treatment also reduced clinical scores (8.50+/-1.96 to 5.40+/-2.12; p < 0.003), but the posttreatment total clinical score of 2,3-dimercapto-1-propanesulfonate-treated patients (3.27+/-1.73) was significantly lower than that of placebo-treated patients (5.40+/-2.12; p < 0.01). The most significant improvement was noted in regard to the clinical scores of weakness, pigmentation, and lung disease. No difference was noted between groups in the hematological and biochemical parameters (which were normal) and skin histology before and after treatment. No 2,3-dimercapto-1-propanesulfonate-related adverse effects were noted. Total urinary excretion of arsenic in 2,3-dimercapto-1-propanesulfonate-treated cases increased significantly following drug therapy, with no increase in placebo-treated cases. CONCLUSION: 2,3-Dimercapto-1-propanesulfonate treatment caused significant improvement in the clinical score of patients suffering from chronic arsenic toxicity. Increased urinary excretion of arsenic during the period of therapy is the possible cause of this improvement.

Adult↗
PubMed2000

Mice lacking in gp91 phox subunit of NAD(P)H oxidase showed glomus cell [Ca(2+)](i) and respiratory responses to hypoxia.

The hypothesis that NAD(P)H oxidase may serve as an oxygen sensor was tested using the mice deficient (knock-out) in gp91phox subunit of NAD(P)H oxidase enzyme complex and compared with wild-type (C57BL/6J) strain measuring the ventilatory and glomus cell intracellular calcium ([Ca(2+)](i)) responses of carotid body to hypoxia. The hypoxic ventilatory responses as well as the [Ca(2+)](i) were preserved in the NAD(P)H oxidase knock-out mice. NAD(P)H oxidase, though a major source of oxygen radical production, is not the oxygen sensor in mice carotid body.

Animals↗
PubMed2000

The metabolic hypothesis revisited.

High levels of CO are used to mimic the stimulatory response of the CSN initiated by hypoxia. Using light of different wavelengths we show that the stimulatory effects of high CO can be pinpointed to the cytochrome c oxidase in the mitochondrial respiratory chain. This supports the metabolic theory of oxygen sensing in the mitochondria.

Animals↗
PubMed2000

Effects of 2,4-dinitrophenol (DNP) on the relationship between the chemosensory activities of the rat carotid body and the intracellular calcium of glomus cells.

To test the hypothesis that the uncoupler 2,4-dinitrophenol (DNP) increases [Ca2+]i equally well, independent of pHi, we studied the effects of 250 microM DNP on [Ca2+]i and carotid sinus nerve (CSN) activity of rat carotid body (CB). CSN activity was measured in CB perfused and superfused with hypocapnic (pHo 7.80) and normocapnic (pHo 7.42) Tyrode solutions. [Ca2+]i of glomus (type I cells) was assessed by superfusion techniques under identical conditions as for CSN recording experiments. The results indicate that 250 microM DNP increased [Ca2+]i of type I cells as well as CSN activity at both pHos, although alkalosis diminished these responses. Given that pHi will change with pHo, DNP did not make any additional pHi change, although [Ca2+]i changed. We conclude that DNP effects were due to [Ca2+]i change alone, and the relationship between [Ca2+]i and CSN activity are internally consistent.

2,4-Dinitrophenol↗
PubMed2000

P(O(2))-P(CO(2)) stimulus interaction in [Ca(2+)](i) and CSN activity in the adult rat carotid body.

Since glomus cell intracellular calcium ([Ca(2+)](i)) plays a key role in generating carotid sinus nerve (CSN) discharge, we hypothesized that glomus cell [Ca(2+)](i) would correspond to CSN discharge rates during P(O(2))-P(CO(2)) stimulus interaction in adult rat carotid body (CB). Accordingly, we measured steady state P(O(2))-P(CO(2)) interaction in CSN discharge rates during hypocapnia (P(CO(2))=8-10 Torr), normocapnia (P(CO(2))=33-35 Torr) and hypercapnia (P(CO(2))=68-70 Torr) in normoxia (P(O(2)) approximately 130 Torr) and hypoxia (P(O(2)) approximately 36 Torr). The results showed P(O(2))-P(CO(2)) stimulus interaction in CSN responses. [Ca(2+)](i) levels were measured in isolated type I cells (2-3 cells/field), using Ca(2+) sensitive fluoroprobe indo-1AM. The [Ca(2+)](i) responses increased with increasing P(CO(2)) in normoxia. In hypoxia, [Ca(2+)](i) did not increase during hypocapnia but increased during normocapnia, showing P(O(2))-P(CO(2)) interaction. However, CSN response during hypoxia was far greater than that for [Ca(2+)](i) response, particularly during hypocapnic hypoxia. Thus, the [Ca(2+)](i) interaction cannot account for the whole CSN interaction. The origin of this CSN P(O(2)-)P(CO(2)) interaction must have occurred in part beyond cellular [Ca(2+)](i) interaction. Interactions at both sites (glomus cell membrane and sinus nerve endings) are reminiscent of reversible O(2)-heme protein reaction with a Bohr effect.

Animals↗
PubMed2000

Separation of carrier-free ytterbium and thulium produced in 80 MeV 12C6+ irradiated gadolinium foil target by liquid-liquid extraction with HDEHP.

Heavy ion activation of natural gadolinium foil with 80 MeV 12C6+ results in the formation of carrier-free ytterbium isotopes, 165,166,167Yb and their corresponding decay products, 165,166,167Tm, in the matrix. Carrier-free ytterbium and thulium isotopes have been separated quantitatively from the bulk target matrix gadolinium by employing di-(2-ethylhexyl)phosphoric acid (HDEHP) as a liquid cation exchanger.

Aluminum↗
PubMed2000

Hepatic damage caused by chronic arsenic toxicity in experimental animals.

OBJECTIVE: Noncirrhotic fibrosis of the liver is common in subjects chronically consuming ground water geologically contaminated with arsenic, but the mechanism of the hepatic fibrosis is not known. Because lipid peroxidation has been implicated in the development of several other forms of hepatic fibrosis, including iron and copper overload, we have explored the roles of oxidative stress and lipid peroxidation in the causation of hepatic fibrosis in a murine model of chronic arsenic toxicity. METHODS: Male BALB/c mice were given drinking water contaminated with arsenic (3.2 mg/L) or arsenic-free (<0.01 mg/L, control) ad libitum. Mice were sacrificed at 3, 6, 9, 12, and 15 months for examination of hepatic histology and assays of hepatic reduced glutathione content, lipid peroxidation, enzymes of the antioxidant defense system, and membrane-bound sodium/potassium ATPase (Na+/K+ ATPase). RESULTS: After 12 months of arsenic feeding, the liver weights increased significantly as did serum aspartate aminotransferase and alanine aminotransferase. After 6 months of arsenic feeding, hepatic glutathione and the enzymes glucose-6-phosphate dehydrogenase and glutathione peroxidase were significantly lower than those of the control group. Hepatic catalase activity was significantly reduced at 9 months in the arsenic-fed group, while glutathione-S-transferase and glutathione reductase activities were also significantly reduced at 12 and 15 months. Plasma membrane Na+/K+ ATPase activity was reduced after 6 months while lipid peroxidation increased significantly after 6 months of arsenic feeding. Liver histology remained normal for the first 9 months, but showed fatty infiltration after 12 months of arsenic feeding. Histologic evidence of fibrosis was observed after 15 months. CONCLUSION: We have demonstrated hepatic fibrosis due to long-term arsenic toxicity in an animal model. Initial biochemical evidence of hepatic membrane damage, probably due to reduction of glutathione and antioxidant enzymes, may be seen by 6 months. Continued arsenic feeding resulted in fatty liver with serum aminotransferase and alanine aminotransferase elevated at 12 months and hepatic fibrosis at 15 months. The murine model is proposed as relevant to epidemic human toxicity in areas of arsenic contamination.

Alanine Transaminase↗
PubMed2000

Altered structure and function of the carotid body at high altitude and associated chemoreflexes.

The ventilatory response to hypoxia is complex. First contact with hypoxia causes an increase in ventilation within seconds that reaches full intensity within minutes because of an increase in carotid sinus nerve (CSN) input to the brain stem. With continued exposure, ventilation increases further over days (ventilatory acclimatization). Initially, it was hypothesized that ventilatory acclimatization arose from a central nervous system (CNS) mechanism. Compensation for alkalosis in the brain and restoration of pH in the vicinity of central chemoreceptors was believed to cause the secondary increase in ventilation. However, when this hypothesis could not be substantiated, attention was turned to the peripheral chemoreceptors. With the lowering of arterial PO2 at high altitude, there is an immediate increase in firing of afferents from chemoreceptors in the carotid body. After peaking over the next few minutes, the firing rate of afferents begins to rise again within hours until a steady state is reached. This secondary increase occurs along with increase in neurotransmitter synthesis and release and altered gene expression followed by hypertrophy of carotid body glomus cells. Further exposure to hypoxia eventually leads to blunting of the CSN output and ventilatory response in some species. This mini review is about the altered structure and function of the carotid body at high altitude and the associated blunting of the chemoreceptor and ventilatory responses observed in some species.

Acclimatization↗
PubMed2000

A profile of the members of FASEB societies: NIH awards, degrees, and institutional affiliations, 1999.

Data from the FASEB Directory of Members and NIH were used to develop a statistical profile of the members of FASEB Societies. For the U.S.-based scientists (exclusive of retired and student members), the most frequently reported degree was a research doctorate (69. 6%). A substantial fraction, however, reported medical degrees (19. 2%) or both research and medical degrees (8.0%). The majority of members of FASEB Societies listed academic affiliations in the directory. Industrial affiliations were reported, however, in 9.7% of the entries with smaller fractions listing associations with hospitals, independent research institutes, and government agencies. Just over one-fourth of the members of FASEB Societies were principal investigators on NIH research grants. These investigators received one-half of all NIH grants and nearly 60% of the RO1 grants.

Awards and Prizes↗
PubMed2000

Historical perspectives of cellular oxygen sensing and responses to hypoxia.

The responses to acute and chronic hypoxia begin with oxygen sensing, and this historical perspective is written in line with this concept. The earliest pertinent work started with studies on fermentation in yeast in the 17th century, before the discovery of oxygen. It required 200 yr to localize the oxygen sensing within the cells and another 100 yr to discover the cellular oxidation reactions. Today, the consensus is that the mitochondrial respiratory chain is in part the site of oxygen sensing. In addition, membrane-bound NAD(P)H oxidase possibly takes part in oxygen sensing. Oxygen-sensing mechanisms occur in a tissue-specific fashion. For example, the carotid body responds to hypoxia promptly by eliciting a ventilatory response, whereas erythropoietin production in response to hypoxia requires more time, involving new expression of genes. The mechanism has therefore moved from the cells to genes.

Animals↗