Health-care scenario in India.
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Delivery of Health Care↗
Biomedical subjects
S K Aggarwal
Publications and source records attributed to S K Aggarwal.
Immune system activation by cisplatin and its analog 'poly-plat': an in vitro and in vivo study.
Swiss Webster mice treated with bolus injections of 'poly-plat' (10 mg/kg) show increased macrophage activation after 2 and 12 days when isolated in cultures. Such macrophages demonstrate an increase in the number of lysosomes and cytoplasmic extension formation with enhanced cytokine (interleukin-1alpha) activity. In addition, peripheral blood smears demonstrated an increase in lymphocytes and monocytes compared to cisplatin-treated animals. These results show that 'poly-plat' activates the immune system more effectively than cisplatin both in vitro and in vivo.
Animals↗
Cisplatin-induced inhibition of the calcium-calmodulin complex, neuronal nitric oxide synthase activation and their role in stomach distention.
Cisplatin (8 mg/kg; i.p.) treatment of Wistar rats produced no change in nitric oxide synthase (NOS) localization or its intensity for up to 5 days. However, immunohistochemically the levels of L-citrulline and the Ca(2+)-calmodulin complex were decreased after only 3 days. An in vitro experiment using an analog of calmodulin. Mero-Calmodulin-1, showed that cis-diammine-diaquacisplatinum(II), a hydrolyzed form of cisplatin, inhibited the calmodulin conformational shift from occurring through a direct interaction with the calmodulin molecule. The results indicate that distention of the stomach was due to inhibition of neuronal NOS activation by a direct interaction between cisplatin and the calcium binding sites of the calmodulin molecule.
Animals↗
Enhanced immunostimulation by novel platinum anticancer agents.
'Poly-plat', SSP and SAP are second generation analogs of cisplatin which have been shown to activate murine peritoneal macrophages in vivo and in vitro. Murine peritoneal macrophages treated with 'poly-plat', SSP or SAP (5 microg/mg) for 2 h are stimulated to form cytoplasmic extensions. Drug-treated macrophages also elicit an increase in the number of lysosomes. In addition, analysis of tissue culture supernatants shows increased levels of interleukin-1alpha and tumor necrosis factor-alpha. These results show that 'poly-plat', SSP and SAP enhance the immune system with greater efficacy and potency than cisplatin.
Adjuvants, Immunologic↗
Activation of murine peritoneal macrophages after cisplatin and taxol combination.
Cisplatin and paclitaxel are potent antineoplastic agents. Their distinctly different mechanisms of action have prompted laboratory and clinical research into their use in combination therapies. Murine peritoneal macrophages treated with cisplatin and paclitaxel in combination elicit an increase in their number of lysosomes. Drug-treated macrophages, when co-incubated with sarcoma 180 cells, establish cytoplasmic contact and transfer lysosomes into tumor cells causing tumor cell lysis. In addition, analysis of tissue culture supernatants show increased levels of interleukin-1alpha and tumor necrosis factor-alpha. Our study shows that cisplatin and paclitaxel in combination enhance elements of the immune system with greater efficacy and potency than when used alone.
Animals↗
Effects of cisplatin and taxol on inducible nitric oxide synthase, gastrin and somatostatin in gastrointestinal toxicity.
Cisplatin (9 mg/kg) or taxol (20 mg/kg) treatment of Wistar rats produced a sharp decrease in inducible nitric oxide synthase (iNOS) and gastrin in the pyloric region of the stomach, and an increase in iNOS and somatostatin in the pancreatic islets. Nitric oxide (NO) functions as a relaxation factor in the smooth muscle of the muscularis mucosa while gastrin plays an important role in the gastroprotection of the mucosa through NO. It is proposed that a decline of the iNOS and gastrin after cisplatin or taxol treatments is related to distention of the stomach, and possibly nausea and vomiting. Hyperglycemia and glucose intolerance after cisplatin treatment may be caused by increases of somatostatin and iNOS in the pancreatic islets. Combination therapy with cisplatin and taxol seems to ameliorate various toxicities due to these two individual drugs.
Animals↗
Role of calcium in modulation of toxicities due to cisplatin and its analogs: a histochemical approach.
Cisplatin, carboplatin and paclitaxel (taxol) are potent antineoplastic agents with associated toxicities, especially gastrointestinal and nephrotoxicity that are their dose-limiting factors in clinical oncology. In an attempt to elucidate their mechanism(s) of toxicity, liver and kidney tissues from normal and drug treated rats and dogs were evaluated for changes in various dehydrogenase and non-specific lipase enzymes. Histochemically, cisplatin treatment induced an inhibition of all the enzymes studied except glucose-6-phosphate dehydrogenase and non-specific lipases, where there was a significant increase. Supplemental treatments with calcium [1 ml of 1.3% CaCl2/day in rats and 2.50 mg (150000 USP units) ergocalciferol plus 1000 mg of elemental calcium as TUMS 500 (EffeCal)/day in dogs] seem to protect against severe gastrointestinal toxicity and nephrotoxicity.
Adenosine Triphosphate↗
Combined left-sided recurrent laryngeal and phrenic nerve palsy after coronary artery operation.
BACKGROUND: Ice/saline slush used along with cold cardioplegia for heart arrest in cardiac operations can cause hypothermic damage to certain structures, an important one being the left phrenic nerve, damage of which results in raised left hemidiaphragm and delayed recovery of the patient. In coronary artery bypass grafting, opening of the pleura and collection of the ice/saline slush in the pleural cavity increases the incidence of injury. METHODS: Three of our nonconsecutive patients underwent coronary artery bypass grafting with cold cardioplegia and open pleura, with collection of ice/saline slush in the pleural cavity for a sufficiently long time. RESULTS: Simultaneous involvement of left recurrent laryngeal nerve along with left phrenic nerve was found in all patients without any concurrent topical injury around the larynx. the recurrent laryngeal nerve took 8 to 10 months to recover. CONCLUSIONS: The left recurrent nerve as it arches around aorta lies in the thorax very close to the parietal pleura and may be prone to hypothermic injury by ice/slush collecting in the pleural cavity during cardiac operations. Judicious use of ice/saline slush had helped in eliminating the problem to some extent.
Aged↗
Contribution of the S4 segment to gating charge in the Shaker K+ channel.
Voltage-activated ion channels respond to changes in membrane voltage by coupling the movement of charges to channel opening. A K+ channel-specific radioligand was designed and used to determine the origin of these gating charges in the Shaker K+ channel. Opening of a Shaker K+ channel is associated with a displacement of 13.6 electron charge units. Gating charge contributions were determined for six of the seven positive charges in the S4 segment, an unusual amino acid sequence in voltage-activated cation channels consisting of repeating basic residues at every third position. Charge-neutralizing mutations of the first four positive charges led to large decreases (approximately 4 electron charge units each) in the gating charge; however, the gating charge of Shaker delta 10, a Shaker K+ channel with 10 altered nonbasic residues in its S4 segment, was found to be identical to the wild-type channel. These findings show that movement of the NH2-terminal half but not the CO2H-terminal end of the S4 segment underlies gating charge, and that this portion of the S4 segment appears to move across the entire transmembrane voltage difference in association with channel activation.
Animals↗
Cost-effectiveness of imaging services in India.
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Cost-Benefit Analysis↗
Cocaine-associated intracranial hemorrhage: absence of vasculitis in 14 cases.
Complications associated with the use of cocaine are varied, and include cerebral hemorrhage and ischemia, with vasculitis and vasospasm as possible etiologies. We reviewed selected brain samples from 14 autopsy cases of cocaine-related cerebrovascular disease. Intracerebral or subarachnoid hemorrhage was present in 12 cases. Intracranial arterioles were either normal or showed nonspecific changes. From these observations, we suggest that intracranial hemorrhages occur in the absence of readily detectable vascular abnormalities.
Adult↗
Determination of blood lead by electron-capture negative chemical ionization gas chromatography-mass spectrometry.
An electron-capture negative chemical ionization (NCI) gas chromatography-mass spectrometry (GC-MS) method for determination of lead (Pb) in blood samples is described. Extraction of Pb from the sample does not involve hot digestion but is based on treatment at ambient temperature. The blood sample is supplemented with a known amount of internal standard (204Pb) for isotope dilution and is treated with concentrated nitric acid. After adjusting the pH to 7, the Pb is extracted into toluene as the pyrrolidine-dithiocarbamate chelate. Samples are then derivatized with 4- fluorophenylmagnesium bromide to form Pb(FC6H4)4. The use of NCI offers enhanced sensitivity (by 75-fold better than previously used electron ionization), gives good precision and accuracy, and has no observable memory effect. The isotope dilution GCoff methodology typically agreed within 2-3% of expected values for the College of American Pathologists blood Pb specimens and the National Institute of Standards and Technology Standard Reference Material 955a.
Gas Chromatography-Mass Spectrometry↗
Capillary gas-liquid chromatography of 6-hydroxylated bile acids.
Gas-liquid chromatographic separation of several bile acids with a hydroxyl group at C-6 is described on two capillary columns, CP-Sil-19 CB and CP-Sil-5 CB. The gas-liquid chromatographic retention indices of bile acids with 6 alpha- and 6 beta-hydroxyl groups are compared with those of bile acids without the C-6 hydroxyl group and the effect of the C-6 hydroxyl group on the retention indices of bile acids is determined. Both 6 alpha- and 6 beta-hydroxyl groups increase the retention index of a bile acid. The retention indices of 6 alpha- or 6 beta-hydroxyl derivatives of chenodeoxycholic acid were found to be higher than those of the corresponding 6-hydroxy derivatives of cholic acid on the CP-Sil-19 CB column but lower on the CP-Sil-5 CB column. Although all 6-hydroxylated derivatives of lithocholic, chenodeoxycholic and cholic acids were not completely resolved on either column alone, combining the two columns resulted in the complete separation of all these compounds.
Bile Acids and Salts↗
Thoracic radicular symptoms in amyotrophic lateral sclerosis.
We report 4 patients with amyotrophic lateral sclerosis (ALS) complaining of thoracic radicular symptoms. We postulate that in some patients paraspinal muscle weakness can result in an increased thoracic kyphosis, possibly producing traction on the thoracic roots.
Aged↗
Cisplatin and carboplatin-mediated activation of murine peritoneal macrophages in vitro: production of interleukin-1 alpha and tumor necrosis factor-alpha.
Analysis of tissue culture supernatants collected from cisplatin (10 micrograms/ml) and carboplatin (50 micrograms/ml)-treated macrophages show enhanced activity of interleukin-1 alpha and tumor necrosis factor-alpha. Cytotoxicity of these supernatants was demonstrated using mouse sarcoma-180 cells. These results demonstrate the ability of cisplatin and carboplatin to enhance the immune system suggestive of yet another mechanism of their action in the regression of tumors.
Animals↗
Spontaneous renal allograft rupture: still a threat.
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Acute Disease↗
Determination of tellurium in urine by isotope dilution gas chromatography/mass spectrometry using (4-fluorophenyl)magnesium bromide as a derivatizing agent and a comparison with electrothermal atomic absorption spectrometry.
The antitumor drug AS-101 [ammoniumtrichloro (dioxoethylene-O,O')tellurate(IV)] is the first tellurium-containing compound that has been identified as possessing immunomodulating properties and minimal toxicity. We have developed a stable isotope dilution gas chromatography/mass spectrometry method using 120Te as an internal standard and (4-fluorophenyl)magnesium bromide as a derivatizing agent for Te determination in urine. The urine samples were digested using HNO3 + H2O2 prior to derivatization with lithium bis(trifluoroethyl)dithiocarbamate at a pH of 3. The trifluorodiethyldithiocarbamate of tellurium was reacted with the Grignard reagent in anhydrous diethyl ether to obtain Te-(FC6H4)2 for GC/MS analysis. All isotope ratio measurements were made by selected ion monitoring with a Finnigan MAT 8230 organic mass spectrometer using a 10-m fused silica capillary column. Overall percision values for the five major Te isotopes relative to 130Te were 0.6-3.1% when 10-ng samples of chelated Te were analyzed. No appreciable memory or carry-over effect was observed when two synthetic mixtures differing in 120Te:130Te ratios by a factor of 50 were sequentially analyzed. The isotope dilution GC/MS method was validated by determining Te in urine samples and comparing the values with electrothermal atomic absorption spectrometry. Te concentrations were determined in the 100-500 micrograms/L range with CVs of 1-4%.
Gas Chromatography-Mass Spectrometry↗
Cisplatin-induced peptic ulcers, vagotomy, adrenal and calcium modulation.
Cytochemical and autoradiographic studies in Wistar rats [Crl:(WI)BR] show that cisplatin treatment (9 mg/kg) inhibits the release of acetylcholine from the axonal endings of the stomach smooth muscle resulting in bloating of the stomach and ulceration. Cisplatin also induces corticosteroid release from the adrenal gland stimulating peptic ulceration. Vagotomy helps ameliorate the effect but not eliminate it. Calcium supplementation restores normal neuromuscular function to gastric smooth muscle, thereby eliminating the gastro-intestinal toxicity due to cisplatin.
Acetylcholinesterase↗