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Biomedical subjects

T Mukherjee

Publications and source records attributed to T Mukherjee.

At least 55 records · Page 3Linked to original sources
PubMed1999

Photophysics of melatonin in different environments.

Melatonin (N-acetyl-5-methoxytryptamine) is a naturally occurring hormone with a structural resemblance to tryptophan. Its fluorescence is solvent dependent and strongly quenched in the presence of oxygen. Fluorescence quenching in aqueous and organic solutions have been studied in the presence of different quenchers. A 1: 1 inclusion complex formation between melatonin and different cyclodextrins in aqueous solution has been observed. The effects of microheterogeneous media provided by cyclodextrins, micelles and reverse micelles on the fluorescence characteristics of melatonin have been investigated. The water-soluble inorganic quenchers like KBr and KI were unable to quench the fluorescence of melatonin dissolved in a microemulsion consisting of surfactant + cyclohexane + 1-propanol + water, whereas the organic quenchers like CCl4 and CHCl3 were able to quench the fluorescence with a rate constant (on the order of 10(8) dm3 mol-1 s-1) quite similar to that in neat organic solvents.

Cyclodextrins↗
PubMed1998

Does beta-carotene protect membrane lipids from nitrogen dioxide?

Lipid peroxidation in rat liver microsomes, induced by nitrogen dioxide (NO2), a free radical toxin, was examined in the absence and in the presence of varying concentrations of beta-carotene. The extent of peroxidation was assayed by determining the malonaldehyde formed as thiobarbituric acid reactive substances (TBARS). When the concentration of beta-carotene was 13.8 and 43.1 nmol/mg protein, no protection was seen, rather an increase of 10% and 30%, respectively, in TBARS was observed as compared with the normal microsomes containing no beta-carotene. However, at beta-carotene concentrations of 66.5 and 89.4 nmol/mg protein, only a marginal increase of 9% and 4% in TBARS, respectively, was observed. The amount of beta-carotene consumed during peroxidation, determined by following the absorbance at 450 nm, was found to increase linearly with increased exposure to NO2. The direct reaction of NO2 with beta-carotene was studied in an inert organic solvent, acetonitrile, by following the absorption spectrum of beta-carotene in the wavelength region 220-600 nm. The rate of loss of beta-carotene was found to be much faster than that in microsomes. The results suggest that in in vitro systems, the reaction of secondary lipid-derived radicals with beta-carotene and their relative competition for NO2 plays an important role in the actual function of beta-carotene as a prooxidant or an antioxidant. Another lipid soluble antioxidant, alpha-tocopherol (vitamin-E), showed significant protection against NO2-induced lipid peroxidation at a concentration of 45 nmol/mg protein under these conditions.

Animals↗
PubMed1998

Altered membrane permeability as the basis of bactericidal action of methdilazine.

The growth inhibition of Escherichia coli and Staphylococcus aureus was accompanied by significant release of K+ and UV-absorbing small molecules upon exposure to methdilazine, an extensively used phenothiazine antihistamine. A severe decrease in [U-14C] glucose uptake and a rapid efflux of hexose from sugar-preloaded bacteria were also observed but without visible cellular lysis. Considerable damage to membrane permeability by methdilazine was proposed to explain the rapid loss in cfu/mL of the bacteria.

Anti-Bacterial Agents↗
PubMed1997

The plasma-membrane Ca2+-ATPase of Leishmania donovani is an extrusion pump for Ca2+.

Controlled exposure of Leishmania donovani promastigotes to hypotonic shock results in the formation of deflagellated unsealed ghosts of original polarity that largely retain the pellicular microtubular structure associated with plasma membrane of the parasite. Gentle shearing followed by suspension of the purified membrane in appropriate isotonic buffer containing Mg2+ (4mM) results in the formation of sealed everted vesicles. The presence of Mg2+ (4 mM) appears to be essential for efficient sealing and also to prevent leakiness. ATP-dependent Ca2+ accumulation can be demonstrated in these vesicles Km values for Ca2+ and ATP were 125 nM and 0.8 mM respectively. The accumulated Ca2+ reaches a concentration of 1.1 mM. Ca2+ uptake is completely inhibited by vanadate (40 microM) and several thiol-modifying agents. Using 5,5'-dithiobis-(2-nitrobenzoic acid) as the modifying agent, an excellent correlation between loss of enzyme activity and transport capability and their parallel regeneration in the presence of 2 mM dithiothreitol was demonstrated. Using 2'.7-bis(carboxyethyl)-5(6)-carboxyfluorescein as the fluorescent pH probe, it was observed that Ca2+ entry into the vesicles is accompanied by an outward movement of H+ from the vesicles. Taken together, this paper establishes that the high-affinity transmembrane Ca2+-ATPase [Ghosh, Ray, Sarkar and Bhaduri (1990) J. Biol. Chem. 265, 11345-11351; Majumdar, Mukherjee, Ray and Bhaduri (1992) J. Biol. Chem. 267, 18440-18446] is an extrusion pump for Ca2+ in this human pathogen.

Adenosine Triphosphate↗
PubMed1997

Endometriosis is not detrimental to embryo implantation in oocyte recipients.

PURPOSE: Our purpose was to determine the effects of endometriosis on implantation and pregnancy rates in ovum recipients. METHODS: The medical records of 239 consecutive oocyte recipient patients who were treated between January 1, 1991, and June 30, 1995, were analyzed retrospectively. Recipients with endometriosis (group 1; n = 55) were compared to recipients without endometriosis (group II; n = 184). Patients in group I had active endometriotic disease confirmed by laparoscopy and were subdivided into mild (Stages I and II; n = 18) and moderate to severe (Stages III and IV; n = 37) endometriosis. RESULTS: No difference was found in recipient age, endometrial thickness, donor age, and embryos transferred. The pregnancy rates (28 versus 29%) and implantation rates (12 and 13%) were also comparable between group I and group II, as well as between patients with mild and patients with moderate to severe endometriosis. CONCLUSIONS: The presence of endometriosis in oocyte recipients does not lower implantation or pregnancy rates. We conclude that the adverse effect of endometriosis on reproductive outcome is not related to implantation but, in fact, is most likely an effect on oocyte or embryo quality.

Adult↗
PubMed1997

Sisters of women with premature ovarian failure may not be ideal ovum donors.

OBJECTIVES: To determine whether the sisters of women with premature ovarian failure (POF) showed a response to gonadotropin stimulation comparable to that of anonymous ovum donors. DESIGN: Historical cohort study. SETTING: Records of 228 consecutive ovum recipients in an academic assisted reproductive technology program. PATIENT(S): Criteria for inclusion were oocyte recipients age < or = 40 years, FSH > 18 mIU/mL (conversion factor to SI unit, 1.00), and/or failure to respond appropriately to controlled ovarian hyperstimulation (COH). Seventy-nine recipients were classified on the basis of whether they received oocytes from anonymous donors (group I, n = 66) or sister donors (group II, n = 13). MAIN OUTCOME MEASURE(S): Controlled ovarian hyperstimulation response, pregnancy rates (PRs), and implantation rates. RESULT(S): The ages of the donors to groups I and II were comparable (31.1 +/- 16.7 versus 29.8 +/- 7.2 years), but those in group II exhibited a higher baseline FSH level (12.8 +/- 2.1 versus 8.6 +/- 5.8 mIU/mL). Group II versus I had a relative risk of 5.1 for cancellation (4 of 13 [30.8%] versus 4 of 66 [6.1%], respectively). In completed cycles of groups I and II, respectively, there was no difference in serum E2 on the day of hCG administration (2,356 +/- 826 versus 1,847 +/- 843 pg/mL; conversion factor to SI unit, 3,671), number of oocytes retrieved (25 +/- 14 versus 22 +/- 13), number of embryos transferred (4.4 +/- 2.1 versus 4.0 +/- 1.0), spontaneous abortion rate (22.7% versus 25.0%), PR (35.5% versus 36.4%), and implantation rate (16.2% versus 16.4%). CONCLUSION(S): There is an increased cancellation rate and, consequently, an overall trend toward decreased ovarian response to gonadotropin stimulation in the sisters of patients with POF. Despite these factors, the implantation rates and PRs of embryos derived from patients reaching retrieval were similar to those from anonymous donors. We recommend counseling women with POF that their sisters may not be ideal ovum donors.

Adult↗
PubMed1996

Biochemical characterization of the 49 kDa penicillin-binding protein of Mycobacterium smegmatis.

The 49 kDa penicillin-binding protein (PBP) of Mycobacterium smegmatis catalyses the hydrolysis of the peptide or S-ester bond of carbonyl donors R1-CONH-CHR2-COX-CHR2-COO- (where X is NH or S). In the presence of a suitable amino acceptor, the reaction partitions between the transpeptidation and hydrolysis pathways, with the amino acceptor, behaving as a simple alternative nucleophile at the level of the acyl-enzyme. By virtue of its N-terminal sequence similarity, the 49 kDa PBP represents one of the class of monofunctional low-molecular-mass PBPs. An immunologically related protein of M(r) 52,000 is present in M. tuberculosis. The 49 kDa PBP is sensitive towards amoxycillin, imipenem, flomoxef and cefoxitin.

Amino Acid Sequence↗
PubMed1996

Pharmacokinetics and toxicokinetics of an orally active tripeptide, IRI-695, in animals.

Pharmacokinetics and toxicokinetics of IRI-695, a tripeptide, were investigated in the rat, rabbit, dog, and monkey. Tissue distribution and excretion of [14C]IRI-695 were determined in the rat. Following a single intravenous (IV) injection, the elimination half-life (t1/2) of IRI-695 in the rabbit, dog, and monkey was similar (about 65 min) and approximately four times that in the rat (15 min). This difference in t1/2 can be attributed to about four times higher clearance of the drug in rats (11.2 mL min-1 kg-1). The volume of distribution (Vss) in these four species, 132-234 mL kg-1, suggested negligible preferential distribution of IRI-695 to body tissue. After a 5 mg kg-1 oral dose, the absolute bioavailability of IRI-695 was 2.0% in rats and 3.1% in dogs. However, systemic drug exposure in the dog was about five to 10 times that in the rat, which is related to the slower clearance of the peptide in the dog. Toxicokinetic studies in the rat and dog indicated linear kinetics and systemic exposure of IRI-695 up to 300 mg kg-1 d-1 oral doses throughout the 28 d toxicity study. Accumulation of the drug after the repeated oral dosing was negligible. After a single 0.10 mg kg-1 [14C]IRI-695 IV injection in rats, almost all of the radioactivity administered was excreted in urine within 24 h postdose.

Amino Acid Sequence↗
PubMed1996

A randomized, placebo-controlled study on the effect of cyclic intermittent etidronate therapy on the bone mineral density changes associated with six months of gonadotropin-releasing hormone agonist treatment.

OBJECTIVE: Our purpose was to determine whether intermittent cyclic etidronate therapy blocks the decline in bone density associated with gonadotropin-releasing hormone agonist therapy. STUDY DESIGN: Thirty-one premenopausal subjects who needed treatment with leuprolide (Lupron) 3.75 mg monthly for 6 months were randomized to etidronate or placebo. Bone turnover was assessed by measurement of serum calcium, phosphorus, alkaline phosphatase, and fasting urinary calcium/creatinine ratios. Bone density was measured by dual energy x-ray absorptiometry. RESULTS: Gonadotropin-releasing hormone treatment produced a significant decrease (4% to 10%) in bone density at the anteroposterior and lateral spine in placebo-treated patients (11). No significant change was demonstrated in etidronate-treated patients (15). Significant increases in serum calcium, phosphorus, alkaline phosphatase, and urinary calcium/creatinine ratios were noted in the placebo group. No significant change in these parameters were evident in the etidronate group. CONCLUSION: Etidronate blocks bone mineral density changes associated with gonadotropin-releasing hormone agonist therapy and normalizes serum and urine indicators of bone turnover.

Adult↗
PubMed1996

An elevated day three follicle-stimulating hormone:luteinizing hormone ratio (FSH:LH) in the presence of a normal day 3 FSH predicts a poor response to controlled ovarian hyperstimulation.

OBJECTIVE: To determine if an elevated FSH:LH ratio predicts response in infertile patients undergoing controlled ovarian hyperstimulation (COH) for IVF-ET. DESIGN: Retrospective study. SETTING: The Division of Reproductive Endocrinology at the Mount Sinai Medical Center, New York, New York. PARTICIPANTS: Seventy-four patients undergoing IVF-ET using similar protocols for COH with day 3 FSH, LH, and E2 testing available for analysis. All patients were < 41 years of age and had day 3 serum FSH < 15 mIU/mL (conversion to SI unit, 1.00). MAIN OUTCOME MEASURES: Follicle-stimulating hormone:LH ratio, day 8 serum E2, peak serum E2, cancellation rate, pregnancy rate, and number and size of follicles. RESULTS: An FSH:LH ratio > or = 3.6 (group I) predicted a poor response to COH (sensitivity 85.7% and specificity 95%). There were no significant differences regarding day 3 serum FSH and ampules of gonadotropins used for COH. Group I (ratio > or = 3.6) patients responded to COH with lower day 8 E2 (97 +/- 18 versus 319 +/- 36 pg/mL; conversion factor to SI unit, 3.671), peak E2 (422 +/- 115 versus 2,368 +/- 183 pg/mL), and fewer follicles > 15 mm (1.3 +/- 0.5 versus 17.1 +/- 1.0). In group I the cycle cancellation rate (12/14) was significantly higher than the group II cycle cancellation rate (2/60) and pregnancy rate in group II (ratio < 3.6) was 25%. CONCLUSIONS: The FSH:LH ratio may increase before a dramatic increase in serum FSH is observed and appears to be a useful marker of ovarian reserve.

Adult↗
PubMed1996

Hydrosalpinx fluid has embryotoxic effects on murine embryogenesis: a case for prophylactic salpingectomy.

OBJECTIVE: To ascertain if hydrosalpinges are associated with reduced pregnancy rates and increased pregnancy loss after IVF-ET. Increased volume and leakage of hydrosalpinx fluid may exert negative effects on follicular development and embryo quality and/or render the uterine environment hostile to embryogenesis. We undertook this study to examine the effect of hydrosalpinx fluid on murine embryogenesis in vitro. DESIGN: Descriptive study. SETTING: Tertiary care facility. PATIENT(S): Premenopausal females undergoing salpingectomy or salpingostomy for hydrosalpinges. INTERVENTION(S): Collection of discarded hydrosalpinx fluid and development of a dose response curve for the effect of hydrosalpinx fluid on murine embryogenesis. MAIN OUTCOME MEASURE(S): Development of single cell mouse embryos in vitro. RESULT(S): All samples of tubal fluid obtained from hydrosalpinges demonstrated a significant embryo toxic effect at either the 100% or 10% concentration. Hydrosalpinx fluid demonstrated pH values (8.45 to 8.65) significantly higher than the physiologic range. Correction of pH to that of media did not affect cavitation rate. CONCLUSION(S): There is a well-defined and significant toxic effect of hydrosalpinx fluid. Procedures such as salpingectomy or proximal tubal occlusion to circumvent the passage of hydrosalpinx fluid into the uterine cavity may have beneficial effects on the developmental environment for embryos in vivo.

Animals↗
PubMed1996

Reactions of OH and eaq- adducts of cytosine and its nucleosides or nucleotides with Cu(II) ions in dilute aqueous solutions: a steady-state and pulse radiolysis study.

The reactions of OH and eaq- adducts of cytosine, cytidine and deoxycytidine in the presence of Cu(II) ions have been studied by product analysis and pulse radiolysis. The product analysis studies show that the degradation of the base is enhanced in N2O-saturated conditions in the presence of Cu(II) ions and the major radiolytic products are Cu(I), cytosine glycols and 5(6)-hydroxycytosine. It is also interesting to note that the yields of Cu(I) are equivalent to cytosine degradation yields, which suggests that the interaction of the OH adducts with Cu(II) ions restricts the radical recombination reactions (known to be the major physicochemical repair process) which partly regenerate the parent cytosine. The rate constants of the reactions of cytosine OH adducts with Cu(II) ions determined by pulse radiolysis lie between 10(7) and 10(8) dm3 mol-1 s-1. The growth in the transient absorption spectra of cytosine OH adducts in the range 330-400 nm, observed in the presence of copper(II) ions in free and complexed state, suggests formation of copper radical adduct which decays by water insertion at the copper-carbon bond to give glycol as the major product. Such copper radical adduct formation was also observed in the case of cytidine and deoxycytidine. The protonated electron adducts (at the hetero atoms) of cytosine, cytidine and deoxycytidine transfer electrons to the Cu(II) ions with rate constants of 10(8) and 10(9) dm3 mol-1 s-1. Here no adduct formation is observed. The steady-state results show that such electron transfer reactions regenerate the parent molecules themselves. Hence such electron transfer reactions do not contribute to enhanced base degradation in the presence of copper ions.

Copper↗
PubMed1995

Severe ovarian hyperstimulation despite prophylactic albumin at the time of oocyte retrieval for in vitro fertilization and embryo transfer.

OBJECTIVE: To report two cases of severe ovarian hyperstimulation syndrome (OHSS) despite the administration of 50 g IV albumin at the time of oocyte retrieval. Two previous published series failed to observe OHSS in patients receiving prophylactic IV albumin. DESIGN: Case reports of two women undergoing controlled ovarian hyperstimulation with E2 > 4,500 pg/mL (conversion factor to SI unit, 3.671) on the day of hCG administration who developed OHSS despite prophylactic albumin administration. SETTING: The division of reproductive endocrinology at the Mount Sinai Medical Center. INTERVENTIONS: Fifty grams IV albumin (200 mL of a 25% albumin solution) were administered over 30 minutes at the time of oocyte retrieval. MAIN OUTCOME MEASURES: Prevention of interstitial fluid accumulation such as ascites, pleural effusions, and generalized edema. The other goals of albumin administration included avoiding hemoconcentration, renal insufficiency, and thrombotic complications. RESULTS: The patients developed sequelae of severe OHSS requiring hospitalization, despite administration of IV albumin. CONCLUSION: Albumin is a promising agent in the prevention of OHSS. However, until the basic pathophysiology of this disorder can be elucidated, the mechanism of its action will remain elusive. Attempts to quantify and report clinical outcomes and the ultimate completion of a prospective randomized study will assist in the prevention and management of this enigmatic disorder.

Adult↗
PubMed1994

Determination of nanogram levels of peptide drug in rabbit and human plasma using high-performance liquid chromatography coupled with electrospray ionization mass spectrometry.

High-performance liquid chromatography (HPLC) coupled to mass spectrometry (MS) using an electrospray ionization (ESI) interface provides a sensitive method for the quantitative analysis of peptide drugs in complex biological matrixes. ESI HPLC-MS was applied to the analysis of a pentapeptide drug (IRI-514) in rabbit and human plasma. Prior to analysis, the plasma samples were prepared using protein precipitation followed by solid-phase extraction. The lower limit of quantitation using selected ion monitoring was determined to be 2 ng/mL, when 8 mL of human plasma spiked with 1-40 ng/mL was extracted. Rabbit plasma (1 mL) samples spiked with 10-40,000 ng of authentic drug/mL gave a linear response when a deuterated peptide analog was employed as an internal standard. A commercial ESI interface was modified to permit higher flow rates (10-20 microL/min) to enter the mass spectrometer source. The revised interface provided a 10-fold increase in sensitivities and permitted the use of standard HPLC columns (2.0-mm i.d.) and HPLC instrumentation. ESI HPLC-MS analysis was automated to provide unattended, precise, and sensitive detection of small peptides in both human and rabbit plasma. Using this methodology, a toxicokinetic study of intravenously administered IRI-514 at three dose levels indicated that the area under the curve values were dose proportional.

Amino Acid Sequence↗