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Biomedical subjects

M Lahav

Publications and source records attributed to M Lahav.

At least 37 records · Page 2Linked to original sources
PubMed1999

Mechanisms underlying endothelin's inhibition of FSH-stimulated progesterone production by ovarian granulosa cells.

In previous studies in porcine granulosa cell cultures, endothelin-1 (ET-1) was shown to inhibit FSH-stimulated cAMP and progesterone accumulation, and to increase inositol phosphate formation and cytosolic calcium ion concentration. The latter results suggest an action of ET-1 via the activation of phospholipase C. Here we have investigated the following experimental questions. (1) Does ET-1 activate PKC in ovarian cells? (2) Does the cellular mechanism(s) whereby ET-1 interferes with the steroidogenic action of FSH in granulosa cells involve an impairment of cAMP generation or action? And (3) how does the site(s) of the inhibitory effect(s) of ET-1 and TPA on FSH-stimulated progesterone accumulation in cultured granulosa cells compare? In the present investigation, ET-1 (1 microM) induced rapid cytosol-to-membrane translocation of [3H]phorbol 12,13-dibutyrate binding sites, indicating protein kinase C (PKC) activation. At 24 or 48 h, ET-1 inhibited FSH-, but not forskolin (1 microM)-induced, cAMP accumulation. Cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc) messenger RNA (mRNA) accumulation was stimulated by FSH, 8-bromo-cAMP (8Br-cAMP, 0.5 mM) and forskolin. ET-1 significantly inhibited this effect of FSH, but not the effects of 8Br-cAMP and forskolin. Progesterone production decreased commensurately with this inhibitory action of ET-1 on the FSH-stimulated accumulation P450scc mRNA. The PKC activator, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), suppressed steroidogenesis stimulated by forskolin and 8Br-cAMP as well as FSH. In conclusion, ET-1 inhibited FSH-stimulated cAMP accumulation, P450scc expression, and progesterone production in porcine granulosa cell cultures. The data are compatible with pre-adenylate cyclase site of action. Although ET-1 activated PKC, TPA, unlike ET-1, seems to inhibit steroidogenesis by interfering with cAMP action.

Animals↗
PubMed1999

Spontaneous Resolution: From Three-Dimensional Crystals to Two-Dimensional Magic Nanoclusters.

In 1848 Louis Pasteur manually separated enantiomorphous three-dimensional crystals. A 2D analogue of this experiment involving clusters of 1-nitronaphthalene bound to a gold surface has been recently performed by the research groups of Berndt and Schneider. The general principles governing separation of enantiomers from 3D crystals to 2D clusters at interfaces, and their characterization, are discussed.

Journal Article↗
PubMed1999

The effect of midazolam premedication on mental and psychomotor recovery in geriatric patients undergoing brief surgical procedures.

UNLABELLED: To assess the effect of IV midazolam premedication on recovery of cognitive function, 90 geriatric patients (aged 65-81 yr) undergoing brief transurethral procedures were enrolled into this prospective, placebo-controlled, double-blinded study. In all cases, a standard general anesthetic was administered. Thirty minutes before operating room transfer, patients in Group 0.5 mg, Group 2 mg, and Group S received 0.5 mg of midazolam, 2 mg of midazolam, or an equal volume of saline, respectively. Before study-drug administration (baseline), at 15 min thereafter, as well as on arrival in the postanesthesia care unit (PACU), and at 60 min and 120 min, postoperatively, we administered a digit-symbol substitution test, a mini-mental test, a shape-sorter test, and a patient-generated 100-mm visual analog score (0 = minimal and 100 = maximal) for anxiety, sleepiness, and coordination. A 4-point scale was used to assess the degree of patient sedation at 7, 15, and 30 min after study-drug administration. Using a modified Aldrete scoring system, PACU discharge was determined by the PACU staff. Patient anxiety, sleepiness, and coordination scores at baseline and at 15 min after study-drug administration were similar. When compared with saline, midazolam was associated with a significantly (P < 0.05) higher incidence of "deep" sedation. In Group 2 mg, the incidence of a low preoperative Spo2 (<94%) was significantly (P < 0.05) higher when compared with Group S. Emergence, extubation, and orientation times, as well as time to follow commands were unaffected by midazolam premedication. Postoperatively, the digit-symbol substitution test, mini-mental test, and shape-sorter test were similar among the groups. However, time to PACU discharge was significantly (P = 0.03) longer in the two midazolam treatment groups (41 +/-25 min, 60 +/- 32 min, 53 +/- 39 min for Groups S, 0.5 mg, and 2 mg, respectively). Finally, patient satisfaction was unaffected by the randomization schedule. IMPLICATIONS: IV premedicant midazolam 0.5 mg or 2 mg does not adversely affect mental and psychomotor recovery in geriatric patients undergoing brief surgical procedures. However, midazolam administration significantly prolonged postanesthesia care unit discharge time. Finally, during the preoperative period, midazolam increases the incidence of a Spo2 <94% in a dose-dependent manner.

Aged↗
PubMed1998

Effects of peripheral-type benzodiazepine receptor antisense knockout on MA-10 Leydig cell proliferation and steroidogenesis.

The peripheral-type benzodiazepine receptor (PBR) is not only widely expressed throughout the body, but it is also genetically conserved from bacteria to humans. Many functions have been attributed to it, but its primary role remains a puzzle. In the current study, we stably transfected cultures of MA-10 Leydig cells with either control or 18-kDa PBR antisense knockout plasmids. The antisense knockout vector was driven by the human enkephalin promoter, which contains two cAMP response elements, such that cAMP treatment of transfected cells could superinduce 18-kDa PBR antisense RNA transcription and, hence, down-regulate endogenous 18-kDa PBR mRNA levels. Control and knockout MA-10 cell lines were then compared at the level of receptor binding, thymidine incorporation, and steroid biosynthesis. Eighteen-kilodalton PBR knockout reduced the maximal binding capacity of tritium-labeled PBR ligands, and the affinity of receptors to the ligands remained unaltered. Additionally, 24-h accumulation of progesterone was lower in the knockout cells. Exposure of the two cell types to 8-bromo-cAMP resulted in a robust increase in steroid production. However, a complex pattern of steroid accumulation was observed, in which further progestin metabolism was indicated. The later decline in accumulated progesterone as well as the synthesis of androstenedione were different in the two cell types. At the level of cell proliferation, reduction of 18-kDa PBR mRNA showed no effect. Thus, we conclude that the 18-kDa PBR may have a more important role in steroidogenesis than in proliferation in this Leydig cell line.

Algestone↗
PubMed1997

Impact of molecular order in langmuir-blodgett films on catalysis

Catalytically active Langmuir-Blodgett films of a rhodium complex were prepared and characterized to determine the possible effect of the molecular order of metal complexes on catalytic activity. The hydrogenation of carbon-oxygen double bonds was used as a model reaction. The complex in solution exhibited low catalytic activity, whereas it was highly active in the film. The catalytic activity was found to be highly dependent on the orientation of the complex within the film. The reactions were also highly selective with regard to the substrate. These observations and the observed rate dependence on temperature strongly implicate the molecular order of a metal complex as an important dimension in catalysis.

Journal Article↗
PubMed1997

Thrombotic complications in essential thrombocythemia with relatively low platelet counts.

Essential thrombocythemia (ET) is often associated with thrombotic and hemorrhagic complications, mostly at platelet counts exceeding 600 x 10(9)/L. There are, however, a few reports of such complications in ET at considerably lower platelet levels and the therapeutic approach to affected patients with relatively low platelet counts is still controversial. In the present study, the first to directly address the issue of hemostatic manifestations at relatively low platelet counts, we have determined the lowest platelet counts associated with such manifestations in 56 consecutive ET patients. Clinical manifestations related to ET were recorded in 46 (82%) patients. Of the symptomatic patients, 32 (70%) had symptoms at platelet counts lower than 600 x 10(9)/L, 23 (50%) at counts lower than 500 x 10(9)/L, 10 (22%) at counts lower than 400 x 10(9)/L, and 6 patients (13%) at platelet counts as low as 300-350 x 10(9)/L. Severe complications occurred at platelet counts lower than 600 x 10(9)/L in 10 patients (22%), lower than 500 x 10(9)/L in 7 (15%), and at lower than 400 x 10(9)/L in 2 (4%). Thrombotic neurologic symptoms were the most common (31 patients, 67%), followed by peripheral vascular symptoms (17 patients, 37%); hemorrhagic complications were relatively rare (3 patients, 7%). In most cases, cessation or improvement of clinical manifestations was observed only after further reduction in platelet counts. In conclusion, thrombotic manifestations, including severe ones, are not uncommon in ET at relatively low platelet counts. We recommend that symptomatic patients with relatively low platelet counts be treated and the platelet counts further reduced well into the lower normal range.

Adult↗
PubMed1997

Retinal safety of oral and topical ofloxacin in rabbits.

Ofloxacin is a broad spectrum fluoroquinolone antibiotic with good ocular penetration. We investigated the potential for retinal toxicity associated with increased intraocular penetration following intensive topical, oral, and combined topical and oral administration. We confirmed ofloxacin concentrations in aqueous and vitreous following these forms of administration. Rabbits received either topical, oral, or a combination of oral and topical ofloxacin. Topical administration consisted of one drop of ofloxacin 0.3% drops given every thirty minutes for a total of eight doses. Oral ofloxacin was administered at a dose of 10 mg (4 mg/kg for average weight 2.5 kg rabbit) every 12 hours for a total of three doses. Six rabbits were followed longitudinally for 4 weeks for evidence of retinal toxicity by indirect ophthalmoscopy and serial ERGs. Electron and light microscopic histopathologic examination of the retina were performed 4 weeks following drug administration. To verify intraocular penetration, ten rabbits received identical dosing schedules followed by HPLC measurement of aqueous and vitreous drug concentrations at 1, 4, 8, 12, and 24 hours following dose completion. No evidence of retinal toxicity was detected by indirect ophthalmoscopy, electroretinography, or histopathological examination. Vitreous ofloxacin levels were highest after combined oral and topical administration, peaking at 0.892 microgram/ml 8 hours following dosage completion. The peak vitreous level following oral administration was 0.230 microgram/ml and 0.026 microgram/ml following topical administration. Peak aqueous humor levels were achieved one hour following drug administration and were 11.400 micrograms/ml after topical, 0.206 microgram/ml after oral, and 8.180 micrograms/ml after combined administration. Our study suggests that intensive topical and oral ofloxacin administration does not cause retinal toxicity in rabbits, despite achieving effective aqueous and vitreous humor antimicrobial concentrations.

Administration, Oral↗
PubMed1997

Long-term vitamin C supplement use and prevalence of early age-related lens opacities.

We designed the present study to examine the cross-sectional relation between age-related lens opacities and vitamin C supplement use over a 10-12-y period before assessment of lens status in women without diagnosed cataract or diabetes. This design avoids biased measurement of nutrient intake that results when knowledge of lens opacities influences nutrition-related behavior or its reporting. The participants were 247 Boston-area women aged 56-71 y selected from the Nurses' Health Study cohort with oversampling of women with high or low vitamin C intakes. Lens opacities were graded with the Lens Opacification Classification System II. Use of vitamin C supplements for > or = 10 y (n = 26) was associated with a 77% lower prevalence of early lens opacities (odds ratio: 0.23; 95% CI: 0.09, 0.60) at any lens site and a 83% lower prevalence of moderate lens opacities (odds ratio: 0.17; 95% CI: 0.03, 0.85) at any lens site compared with women who did not use vitamin C supplements (n = 141) after adjustment for age and other potentially confounding variables. Women who consumed vitamin C supplements for < 10 y showed no evidence of a reduced prevalence of early opacities. These data, together with data from earlier experimental and epidemiologic studies, suggest that long-term consumption of vitamin C supplements may substantially reduce the development of age-related lens opacities.

Adult↗
PubMed1996

Formation of Chiral Interdigitated Multilayers at the Air-Liquid Interface Through Acid-Base Interactions

Thin interdigitated films composed of a long-chain, water-insoluble chiral acid (p-pentadecylmandelic acid of absolute configuration R) and a water-soluble chiral base (phenylethylamine, R') were constructed at the air-solution interface. The (R, R') structure was characterized to near-atomic resolution by grazing-incidence x-ray diffraction (GIXD). The two diastereomeric systems, (R, R') and (R, S'), demonstrate similar surface pressure-molecular area isotherms, but their structures are completely different on the molecular level, as monitored by GIXD. Complementary data on these two architectures were provided by atomic force microscopy.

Journal Article↗
PubMed1996

Severe myelotoxicity of oral etoposide in heavily pretreated patients with non-Hodgkin's lymphoma or chronic lymphatic leukemia.

BACKGROUND: Promising results have been reported for patients with non-Hodgkin's lymphoma (NHL) receiving chronic oral etoposide. Due to the small number of patients reported, information regarding side effects is limited, and therefore warrants further evaluation. METHODS: Twenty eligible patients with NHL and chronic lymphatic leukemia (CLL), resistant to or relapsed after previous protocols of polychemotherapy were treated with oral etoposide at a dosage of 50 mg/m2/day for 21 days in a 28-day cycle. Response and toxicity were evaluated according to standard criteria. RESULTS: Total response was noted in 13 patients, complete response in 2 patients, and partial response in 11 patients. Two patients had stable disease and five patients had progression of disease during treatment. Seventy-five percent of patients experienced neutropenia below 1500/microL. Half acquired infection and required hospitalization. Fifty-five percent required blood transfusions. All patients needed course shortening and dosage reduction. CONCLUSIONS: Chronic daily administration of oral etoposide is effective in patients with NHL and CLL. In heavily pretreated patients, myelotoxicity is severe. Therefore, modification of the schedule plan is mandatory in this group of patients.

Adult↗
PubMed1996

Paradoxical effect of 3-isobutyl-1-methylxanthine on cytochrome P450 cholesterol side-chain cleavage mRNA accumulation in porcine granulosa cells.

Earlier studies in immature porcine granulosa cells cultured in serum-free medium showed dual actions of the protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA). In cells incubated for 24 h, TPA inhibited follicle-stimulating hormone (FSH)-stimulated cytochrome P450 cholesterol side-chain cleavage (P450scc) mRNA accumulation. In contrast, at 4 h, TPA increased P450scc mRNA concentration in the absence and presence of FSH or 8-bromo-cAMP; in addition, TPA augmented FSH-stimulated cAMP accumulation. The actions of TPA were then examined in the presence of the phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX). With IBMX present, TPA caused a smaller relative augmentation of cAMP accumulation during a 4-h incubation period, suggesting that TPA may both increase cAMP synthesis and inhibit its degradation. The stimulatory effect of FSH or 8-bromo-cAMP on P450scc mRNA concentration was not modified by IBMX. However, TPA no longer augmented the FSH- or 8-bromo-cAMP-stimulated P450scc mRNA accumulation when IBMX was present. In cells treated with FSH for 24 h, IBMX augmented progesterone production, but paradoxically accentuated the inhibitory effect of TPA on steroidogenesis. These results indicate that IBMX converts TPA from a stimulatory into an inhibitory agent by an action unrelated to cAMP, and points to the need for caution in interpreting experiments with this drug.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Ocular toxicity following topical application of anesthetic cream to the eyelid skin.

BACKGROUND AND OBJECTIVE: The use of topical anesthetic cream in the periorbital region may be of clinical value. The potential for toxic effects from such use has not been studied in a controlled manner. This study was performed to evaluate the potential ocular toxicity of anesthetic cream topically applied to the eyelid in an animal model. MATERIALS AND METHODS: Ten rabbits underwent periorbital eutectic mixture of local anesthetics (EMLA) (2.5 percent lidocaine and 2.5 percent prilocaine) application and were observed for evidence of gross or microscopic ocular toxicity. Baseline external and anterior segment examinations were performed, including biomicroscopy and fluorescein staining, after which a standard quantity of EMLA cream (0.75 g) was applied along the upper eyelid and covered with an occlusive dressing. After 1 hour of treatment, the eyelid and anterior segment were examined for evidence of adverse reaction. The eyelids were excised and examined histopathologically. RESULTS: No significant adverse effects were noted on external lid and anterior segment examination. The histopathologic findings were within normal limits. CONCLUSIONS: This study suggests that external application of EMLA cream to the eyelid does not induce local toxicity in the rabbit model. The external application of EMLA cream may be safe in the periorbital region.

Administration, Topical↗
PubMed1995

Combined dacryops with underlying benign mixed cell tumor of the lacrimal gland.

PURPOSE/METHODS: Computed tomographic scan disclosed a well-defined mass in the right lacrimal fossa of a 57-year-old woman. We excised and examined the mass. RESULTS/CONCLUSIONS: The mass was a combination of a small benign mixed cell tumor and a large ductal cyst of the lacrimal gland. It is possible that a cyst in the lacrimal duct may mask an underlying neoplasm of the lacrimal gland.

Adenoma, Pleomorphic↗
PubMed1995

Clomiphene citrate reduces procarbazine-induced sterility in a rat model.

Chemotherapy with the cytotoxic drug procarbazine (PCB) causes permanent infertility in most male patients. Since many patients treated with this cytotoxic drug are of reproductive age, it is important to develop a method to protect spermatogenesis and fertility. It has been hypothesised that 'spermatogenic arrest' by pharmacological intervention may render the testes less susceptible to the effects of chemotherapy. The present study investigated whether recovery of fertility in a male rat model could be achieved by suppression of spermatogenesis with high doses of clomiphene citrate (CC) prior to PCB administration. It was demonstrated that young male rats treated with a combination of CC and PCB partially recovered spermatogenesis and achieved almost normal fertility. In contrast, animals treated with PCB alone exhibited abnormal spermatogenesis and remained infertile.

Animals↗
PubMed1995

Dual actions of phorbol ester on cytochrome P450 cholesterol side-chain cleavage messenger ribonucleic acid accumulation in porcine granulosa cells.

In earlier studies in cultures of porcine granulosa cells prepared from small antral follicles, steroidogenesis-related loci were inhibited by treatment for 48 h with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a potent activator of protein kinase C (PKC). In the present investigation, cells were incubated in serum-free medium for 48 h, with various agents present during the last 2-24 h. With TPA at 30 ng/ml, the FSH-stimulated cAMP accumulation was markedly enhanced at all time points. FSH increased the concentration of cytochrome P450 cholesterol side-chain cleavage (P450scc) mRNA throughout the 24-h incubation. At 4 and 8 h, TPA increased the accumulation of P450scc mRNA, having an additive effect with FSH. However, at 24 h, TPA markedly suppressed the FSH-induced increased in P450scc mRNA. Pretreatment of cells with FSH did not shorten the time required for TPA to become inhibitory. The stimulatory effect of 8-bromo-cAMP on P450scc mRNA also was augmented by TPA at 4 h, but significant inhibition was not observed at 24 h. The concentration of glyceraldehyde-3-phosphate dehydrogenase mRNA, intended to be used for correction of gel loading, was stably increased by both cAMP and TPA. These effects of TPA suggest multiple actions of PKC(s) on the regulation of P450scc expression and other endpoints in ovarian granulosa cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Interferon alpha-2b modulates beta-galactoside alpha-2,6-sialyltransferase gene expression in rat testes.

Sperm surface glycoproteins are modified during passage through the epididymis, a process believed to be important in the production of functionally mature spermatozoa. The effect of various cytokines on reproductive events has recently been investigated, with conflicting results. In the present investigation, the effect of interferon-alpha-2b (IFN alpha 2b) on sialyltransferase (ST) activity and beta-galactoside alpha-2,6-sialyltransferase (Gal 2,6-ST) mRNA expression was studied in rat testicular tissue. The results revealed the presence of Gal 2,6-ST mRNA in rat testicular tissue, similar in molecular size to that found previously in rat spleen, lung, ovary, kidney, heart, and brain. In addition, we observed that IFN alpha 2b reduced Gal 2,6-ST mRNA and ST activity in rat testes by a comparable magnitude. These findings provide insight into an additional mechanism by which cytokines may affect the reproductive system.

Animals↗