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Biomedical subjects

K Sriram

Publications and source records attributed to K Sriram.

At least 19 recordsLinked to original sources
PubMed2006

Compositional complementarity and prebiotic ecology in the origin of life.

We hypothesize that life began not with the first self-reproducing molecule or metabolic network, but as a prebiotic ecology of co-evolving populations of macromolecular aggregates (composomes). Each composome species had a particular molecular composition resulting from molecular complementarity among environmentally available prebiotic compounds. Natural selection acted on composomal species that varied in properties and functions such as stability, catalysis, fission, fusion and selective accumulation of molecules from solution. Fission permitted molecular replication based on composition rather than linear structure, while fusion created composomal variability. Catalytic functions provided additional chemical novelty resulting eventually in autocatalytic and mutually catalytic networks within composomal species. Composomal autocatalysis and interdependence allowed the Darwinian co-evolution of content and control (metabolism). The existence of chemical interfaces within complex composomes created linear templates upon which self-reproducing molecules (such as RNA) could be synthesized, permitting the evolution of informational replication by molecular templating. Mathematical and experimental tests are proposed.

Biological Evolution↗
PubMed2004

A two variable delay model for the circadian rhythm of Neurospora crassa.

A two variable model with delay in both the variables, is proposed for the circadian oscillations of protein concentrations in the fungal species Neurospora crassa. The dynamical variables chosen are the concentrations of FRQ and WC-1 proteins. Our model is a two variable simplification of the detailed model of Smolen et al. (J. Neurosci. 21 (2001) 6644) modeling circadian oscillations with interlocking positive and negative feedback loops, containing 23 variables. In our model, as in the case of Smolen's model, a sustained limit cycle oscillation takes place in both FRQ and WC-1 protein in continuous darkness, and WC-1 is anti-phase to FRQ protein, as observed in experiments. The model accounts for various characteristic features of circadian rhythms such as entrainment to light dark cycles, phase response curves and robustness to parameter variation and molecular fluctuations. Simulations are carried out to study the effect of periodic forcing of circadian oscillations by light-dark cycles. The periodic forcing resulted in a rich bifurcation diagram that includes quasiperiodicity and chaotic oscillations, depending on the magnitude of the periodic changes in the light controlled parameter. When positive feedback is eliminated, our model reduces to the generic one dimensional delay model of Lema et al. (J. Theor. Biol. 204 (2000) 565), delay model of the circadian pace maker with FRQ protein as the dynamical variable which represses its own production. This one-dimensional model also exhibits all characteristic features of circadian oscillations and gives rise to circadian oscillations which are reasonably robust to parameter variations and molecular noise.

Circadian Rhythm↗
PubMed2004

Bedside emergency ultrasonographic diagnosis of diaphragmatic rupture in blunt abdominal trauma.

Abdominal injury from significant blunt trauma can include injury to bowel, kidneys, liver, and spleen. In approximately 5% of all injuries one of the diaphragms is ruptured. Diaphragmatic rupture may not be easily detected and this can lead to significant morbidity and even mortality. Rupture may be suggested on chest X-ray film especially with abnormal nasogastric tube location but the accuracy of this method is modest only. Abdominal computed tomography is not accurate and magnetic resonance imaging, although very sensitive and specific, is not feasible in most trauma situations. Surgeons have often resorted to exploratory laparotomy or laparoscopy to make the diagnosis. Although not typically part of the basic Focused Abdominal Sonography for Trauma (FAST) examination, ultrasonographic diagnosis of diaphragmatic rupture is possible with little added time to the examination. We present 3 cases of diaphragmatic rupture discovered shortly after the patients' arrival, on initial trauma evaluation with the FAST. A discussion of previous literature and ultrasound technique for diagnosis follows the cases.

Abdominal Injuries↗
PubMed2004

A baseline study of rural Bancroftian filariasis in southern India.

Night mass blood surveys were carried out for parasitological evidence of Bancroftian filariasis in 45 rural areas belonging to 9 National Filaria Control Program (NFCP) zones of East Godavari and West Godavari districts of Andhra Pradesh, India during the period 1998 to 2001. Mf prevalence range between 2.9 to 10.2%, and mf intensities in 20 mm3 blood samples ranged from 1-281. The present study explains the trend of microfilaria dynamics in the rural population, where mass drug delivery has been implemented since 1997, and anti-larivicidal and adulticidal control measures have not been adopted.

Adolescent↗
PubMed2002

Obesity exacerbates chemically induced neurodegeneration.

Obesity is a major risk factor associated with a variety of human disorders. While its involvement in disorders such as diabetes, coronary heart disease and cancer have been well characterized, it remains to be determined if obesity has a detrimental effect on the nervous system. To address this issue we determined whether obesity serves as a risk factor for neurotoxicity. Model neurotoxicants, methamphetamine (METH) and kainic acid (KA), which are known to cause selective neurodegeneration of anatomically distinct areas of the brain, were evaluated using an animal model of obesity, the ob/ob mouse. Administration of METH and KA resulted in mortality among ob/ob mice but not among their lean littermates. While METH caused dopaminergic nerve terminal degeneration as indicated by decreased striatal dopamine (49%) and tyrosine hydroxylase protein (68%), as well as an increase in glial fibrillary acidic protein by 313% in the lean mice, these effects were exacerbated under the obese condition (96%, 86% and 602%, respectively). Similarly, a dosage of KA that did not increase glial fibrillary acidic protein in lean mice increased the hippocampal content of this protein (93%) in ob/ob mice. KA treatment resulted in extensive neuronal degeneration as determined by Fluoro-Jade B staining, decreased hippocampal microtubule-associated protein-2 immunoreactivity and increased reactive gliosis in ob/ob mice. The neurotoxic outcome in ob/ob mice remained exacerbated even when lean and ob/ob mice were dosed with METH or KA based only on a lean body mass. Administration of METH or KA resulted in up-regulation of the mitochondrial uncoupling protein-2 to a greater extent in the ob/ob mice, an effect known to reduce ATP yield and facilitate oxidative stress and mitochondrial dysfunction. These events may underlie the enhanced neurotoxicity seen in the obese mice. In summary, our results implicate obesity as a risk factor associated with chemical- and possibly disease-induced neurodegeneration.

Animals↗
PubMed2002

Seasonal prevalence of Culex vishnui subgroup, the major vectors of Japanese encephalitis virus in an endemic district of Andhra Pradesh, India.

Seasonal prevalence of members of the Culex vishnui subgroup, the major vectors of Japanese encephalitis virus (JE) in an endemic district of Andhra Pradesh, was investigated. Approximately 15,500 mosquitoes belonging to 2 genera and 5 species were collected by indoor-resting collections. The predominant species were found to be from the Cx. vishnui subgroup, which comprised 42.6% of the total collection, followed by Anopheles subpictus (40.4%), An. hyrcanus (12.8%), Cx. gelidus (3.5%), and An. barbirostris (0.8%). Mosquitoes of the Cx. vishnui subgroup were collected throughout the year, and densities of females ranged from 2.3/man-hour in January 1999 to 26.0/man-hour in December 1999. Ninety-three cases of Japanese encephalitis (27 confirmed serologically) were reported, mainly during the monsoon months of November and December. A significant positive correlation between densities of mosquitoes of the Cx. vishnui subgroup and occurrence of Japanese encephalitis cases (r = 0.765, P < 0.01) was observed. The factors responsible for transmission of JE in the endemic district are discussed.

Animals↗
PubMed2002

Relative abundance of Culex quinquefasciatus (Diptera: Culicidae) with reference to infection and infectivity rate from the rural and urban areas of East and West Godavari districts of Andhra Pradesh, India.

This paper describes the seasonal abundance of Culex quinquefasciatus in the rural and urban areas of the East and West Godavari districts (EGDT and WGDT) of Andhra Pradesh, India. The per man-hour density (PMHD) was collected from seven units in EGDT and two units in WGDT, which comprised rural and urban areas. The highest infection and infectivity rates were found in the rural areas of Rajahmundry (43.6%) and Amalapuram (13.2%) respectively. In urban areas, the highest infection and infectivity rates were found in Rajahmundry: 7.5% and 3.6% respectively. There was considerable difference in the infection rate and infectivity rates between the rural areas and urban areas in each unit.

Analysis of Variance↗
PubMed2000

Extended indications for enteral nutritional support.

With the availability of an organized nutrition support team (NST), the use of enteral nutrition (EN) can be extended to patients who would have otherwise received parenteral nutrition (PN). Although the formulation and accuracy of nutrient intake seems easier with PN, it is accepted that EN is cost effective and advantageous and should be used whenever possible. We discuss three cases in which the NST was initially consulted to provide PN. After evaluation by the dietitian, gastrointestinal access was obtained by the NST physician and EN could be initiated. The case studies show that an organized NST consisting of knowledgeable members can extend the use of EN to patients who would have otherwise received PN. The cost saving of such an approach and its efficacy in clinical practice are obvious.

Adult↗
PubMed1999

Short-course chemotherapy for tuberculosis of the spine. A comparison between ambulant treatment and radical surgery--ten-year report.

We performed a randomised, controlled clinical trial to compare ambulant short-course chemotherapy with anterior spinal fusion plus short-course chemotherapy for spinal tuberculosis without paraplegia. Patients with active disease of vertebral bodies were randomly allocated to one of three regimens: a) radical anterior resection with bone grafting plus six months of daily isoniazid plus rifampicin (Rad6); b) ambulant chemotherapy for six months with daily isoniazid plus rifampicin (Amb6); or c) similar to b) but with chemotherapy for nine months (Amb9). Ten years from the onset of treatment, 90% of 78 Rad6, 94% of 78 Amb6 and 99% of 79 Amb9 patients had a favourable status. Ambulant chemotherapy for a period of six months with daily isoniazid plus rifampicin (Amb6) was an effective treatment for spinal tuberculosis except in patients aged less than 15 years with an initial angle of kyphosis of more than 30 degrees whose kyphosis increased substantially.

Adolescent↗
PubMed1998

Thiol oxidation and loss of mitochondrial complex I precede excitatory amino acid-mediated neurodegeneration.

Human ingestion of "chickling peas" from the plant Lathyrus sativus, which contains an excitatory amino acid, L-BOAA (L-beta-N-oxalylamino-L-alanine), leads to a progressive corticospinal neurodegenerative disorder, neurolathyrism. Exposure to L-BOAA, but not its optical enantiomer D-BOAA, causes mitochondrial dysfunction as evidenced by loss of complex I activity in vitro in male mouse brain slices and in vivo in selected regions of mouse CNS (lumbosacral cord and motor cortex). Loss of complex I activity in lumbosacral cord after L-BOAA administration to mice was accompanied by concurrent loss of glutathione. The inhibited complex I activity in mitochondria isolated from lumbosacral cord of animals treated with L-BOAA rebounded after incubation with the thiol-reducing agent dithiothreitol, indicating that oxidation of protein thiols to disulfides was responsible for enzyme inhibition. The inhibition of complex I could be abolished by pretreatment with antioxidant thiols such as glutathione ester and alpha-lipoic acid. Chronic treatment of male mice, but not female mice, with L-BOAA resulted in loss of complex I activity and vacuolation and dendritic swelling of neurons in the motor cortex and lumbar cord, paralleling the regionality of the aforementioned biochemical effects on CNS mitochondria. These results support the view that thiol oxidation and concomitant mitochondrial dysfunction (also implicated in other neurodegenerative disorders), occurring downstream of glutamate receptor activation by L-BOAA, are primary events leading to neurodegeneration. Maintenance of protein thiol homeostasis by thiol delivery agents could potentially offer protection against excitotoxic insults such as those seen with L-BOAA.

Amino Acids, Diamino↗
PubMed1997

Evidence for generation of oxidative stress in brain by MPTP: in vitro and in vivo studies in mice.

The role of oxidative stress in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mediated neurotoxicity is as yet unclear and the evidence for generation of oxygen free radicals as a primary event in the neurotoxicity is yet to be demonstrated. The present study was undertaken to ascertain the potential role of oxidative damage, and the protective role, if any, of the antioxidant, glutathione (GSH), in MPTP-induced neurotoxicity. Exposure of sagittal slices of mouse brain to MPTP resulted in significant increases of reactive oxygen species (ROS) and malondialdehyde (MDA, the product of lipid peroxidation) and decreases in GSH content. Pretreatment of mouse brain slices, in vitro, with GSH or GSH isopropyl ester attenuated MPTP toxicity as assessed by the tissue activity of the mitochondrial enzyme, NADH-dehydrogenase (NADH-DH), and by leakage of the cytosolic enzyme, lactate dehydrogenase (LDH), from the slice into the medium. In vivo administration of MPTP (30 mg/kg body weight, s.c.), to mice resulted in significant lowering of GSH in the striatum and midbrain, 2 h after dosage; ROS levels in the striatum and midbrain increased after 4 and 8 h, respectively. In the striatum significant inhibition of rotenone-sensitive NADH ubiquinone-1 oxido-reductase (Complex 1) was observed transiently 1 h after MPTP administration. The enzyme activity recovered thereafter; significant inhibition of mitochondrial Complex I was observed in the striatum only 18 h after MPTP dose. In the midbrain, mitochondrial Complex I was inhibited only 18 h after MPTP dose; no change was observed at the early time points examined. Thus, the depletion of GSH and increased ROS formation preceded the inhibition of the mitochondrial enzyme in the midbrain. Evidence presented herein from both in vitro and in vivo studies support that MPTP exposure generates ROS resulting in oxidative stress.

Animals↗
PubMed1997

In vitro neurotoxicity of the antitumor agent 9-methoxy-N2-methylellipticinium acetate (MMEA): role of brain cytochrome P-450.

9-methoxy-N2-methylellipticinium acetate (MMEA) is representative of a series of quaternized ellipticine derivatives that are selectively cytotoxic to human brain tumor cell lines derived from non-neuronal (glial) cells (Acton et al, 1994). In an attempt to determine whether MMEA may exhibit toxicity to normal brain cells, we have examined the effect of the drug, in vitro, using sagittal slices of rat brain. Incubation of rat brain slices in an artificial cerebrospinal fluid medium containing MMEA resulted in dose-dependent leakage of lactate dehydrogenase (LDH) into the surrounding medium. However, other subcellular marker enzymes such as Na(+)-K+ATPase (plasma membrane), cytochrome c oxidase, isocitrate dehydrogenase, NADH-dehydrogenase (mitochondrial), N-acetylglucosaminidase, acid phosphate (lysosomal), glyceraldehyde-3-phosphate dehydrogenase and enolase (glycolytic enzymes) were unaffected even at the highest tested concentrations of MMEA (10 and 100 microM). Preincubation of slices with reserpine (1 nM) or, dopamine or serotonin-specific reuptake inhibitors abolished MMEA-induced toxicity in brain slices. Pretreatment of slices with piperonyl butoxide and metyrapone, inhibitor of cytochrome P-450, also prevented the toxicity of MMEA. Further, brain slices prepared from phenobarbital-treated rats showed enhanced sensitivity to MMEA; significant leakage of LDH was observed at MMEA concentrations as low as 1 nM. The present studies demonstrate the toxicity of MMEA in rat brain slices, in vitro, and suggest a role for brain cytochrome P-450 in the neurotoxicity of MMEA [corrected].

Animals↗
PubMed1997

Late onset paraplegia--a sequela to Pott's disease. A report on imaging, prevention and management.

Late onset paraplegia is a neurological complication that develops after a variable period in a patient with healed tuberculous disease of the vertebrae. In this retrospective analysis clinical features, imaging in diagnosis and treatment of this condition are described among 5 cases seen over a period of 5 years. This complication occurred even after successful treatment of initial spinal lesions with rifampicin-containing regimens. Magnetic resonance imaging was useful in pinpointing the exact pathology; one case had syrinx and two cases had marked internal gibbus with cord atrophy. Of the two cases who accepted surgical treatment, one improved.

Adolescent↗
PubMed1996

Gastroduodenal decompression and simultaneous nasoenteral nutrition: "extracorporeal gastrojejunostomy".

The term "extracorporeal gastrojejunostomy" is being proposed to connote the process of refeeding gastric aspirates along with enteral nutritional support administered distally into the duodenum or jejunum. Although the procedure itself is common and known to clinicians, it is believed that the introduction and popularization of this unusual expression will heighten awareness of this approach. This can be achieved by using one multilumen tube or two tubes, one for gastric aspiration and one for distal feeding.

Aged↗