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Biomedical subjects

M Ben-David

Publications and source records attributed to M Ben-David.

At least 19 recordsLinked to original sources

Running energetics of the North American river otter: do short legs necessarily reduce efficiency on land?

Semi-aquatic mammals move between two very different media (air and water), and are subject to a greater range of physical forces (gravity, buoyancy, drag) than obligate swimmers or runners. This versatility is associated with morphological compromises that often lead to elevated locomotor energetic costs when compared to fully aquatic or terrestrial species. To understand the basis of these differences in energy expenditure, this study examined the interrelationships between limb morphology, cost of transport and biomechanics of running in a semi-aquatic mammal, the North American river otter. Oxygen consumption, preferred locomotor speeds, and stride characteristics were measured for river otters (body mass=11.1 kg, appendicular/axial length=29%) trained to run on a treadmill. To assess the effects of limb length on performance parameters, kinematic measurements were also made for a terrestrial specialist of comparable stature, the Welsh corgi dog (body mass=12.0 kg, appendicular/axial length=37%). The results were compared to predicted values for long legged terrestrial specialists. As found for other semi-aquatic mammals, the net cost of transport of running river otters (6.63 J kg(-1)min(-1) at 1.43 ms(-1)) was greater than predicted for primarily terrestrial mammals. The otters also showed a marked reduction in gait transition speed and in the range of preferred running speeds in comparison to short dogs and semi-aquatic mammals. As evident from the corgi dogs, short legs did not necessarily compromise running performance. Rather, the ability to incorporate a period of suspension during high speed running was an important compensatory mechanism for short limbs in the dogs. Such an aerial period was not observed in river otters with the result that energetic costs during running were higher and gait transition speeds slower for this versatile mammal compared to locomotor specialists.

Animals↗

Characteristics of sex-biased dispersal and gene flow in coastal river otters: implications for natural recolonization of extirpated populations.

River otters (Lontra canadensis) were extirpated from much of their historic distribution because of exposure to pollution and urbanization, resulting in expansive reintroduction programmes that continue today for this and other species of otters worldwide. Bioaccumulation of toxins negatively affects fecundity among mustelids, but high vagility and different dispersal distances between genders may permit otter populations to recover from extirpation caused by localized environmental pollution. Without understanding the influence of factors such as social structure and sex-biased dispersal on genetic variation and gene flow among populations, effects of local extirpation and the potential for natural recolonization (i.e. the need for translocations) cannot be assessed. We studied gene flow among seven study areas for river otters (n = 110 otters) inhabiting marine environments in Prince William Sound, Alaska, USA. Using nine DNA microsatellite markers and assignment tests, we calculated immigration rates and dispersal distances and tested for isolation by distance. In addition, we radiotracked 55 individuals in three areas to determine characteristics of dispersal. Gender differences in sociality and spatial relationships resulted in different dispersal distances. Male river otters had greater gene flow among close populations (within 16-30 km) mostly via breeding dispersal, but both genders exhibited an equal, low probability of natal dispersal; and some females dispersed 60-90 km. These data, obtained in a coastal environment without anthropogenic barriers to dispersal (e.g. habitat fragmentation or urbanization), may serve as baseline data for predicting dispersal under optimal conditions. Our data may indicate that natural recolonization of coastal river otters following local extirpation could be a slow process because of low dispersal among females, and recolonization may be substantially delayed unless viable populations occurred nearby. Because of significant isolation by distance for male otters and low gene flow for females, translocations should be undertaken with caution to help preserve genetic diversity in this species.

Alaska↗

Response of river otters to experimental exposure of weathered crude oil: fecal porphyrin profiles.

Profiles of porphyrins were characterized in fecal samples from river otters (Lontra canadensis) experimentally exposed to weathered crude oil to determine effects on heme synthesis. Fifteen male river otters were randomly assigned to three groups of five individuals each representing a control group, a low-dosage group that received 5 mg/kg body mass of oil per day, and a high-dosage group that received 50 mg/kg body mass of oil per day. Mean levels of coproporphyrin III (CoproIII) and protoporphyrin IX (ProtoIX) in fecal samples collected from all experimental river otters were higher throughout the experimental period than levels of CoproIII and ProtoIX in fecal samples collected previously at two field sites. No statistically significant differences in levels of CoproIII and ProtoIX were observed between treatment groups, although a trend of reduction in variability in CoproIII was observed in the low- and high-dose groups. We found no relation between levels of CoproIII and ProtoIX, suggesting that the process of disruption that leads to oxidation of the precursors of porphyrins is probably nonlinear. Our results also indicate that the interaction between oiled induced reduction in hemoglobin levels and induction of CYP1A1 corresponded with significantly lower levels of ProtoIX in the fecal samples, possibly representing high demand for ProtoIX. Therefore, while this experiment does not support the use of porphyrin profiles as an individual biomarker, it does suggest that the latter may be valuable when a weight of evidence is used in an ecotoxicological risk assessment in which the interactions between several biomarkers are explored.

Animals↗

Biomarker responses in river otters experimentally exposed to oil contamination.

Investigations in Prince William Sound (Alaska, USA) following the Exxon Valdez oil spill (EVOS) revealed that river otters (Lontra canadensis) on oiled shores had lower body mass and elevated values of biomarkers, than did otters living on nonoiled shores. In addition, otters from oiled areas selected different habitats, had larger home ranges, and less diverse diets than animals living in nonoiled areas. These differences between river otters from oiled shores and those from nonoiled areas strongly suggested that oil contamination had an effect on physiological and behavioral responses of otters. In this study, we explored the effects of crude oil contamination on river otters experimentally. We hypothesized that exposure to oil would result in elevated values of biomarkers, indicating induced physiological stress. Fifteen wild-caught male river otters were exposed to two levels of weathered crude oil (i.e., control, 5 ppm/day/kg body mass, and 50 ppm/day/kg body mass) under controlled conditions in captivity at the Alaska Sealife Center in Seward (Alaska, USA). Responses of captive river otters to oil ingestion provided mixed results in relation to our hypotheses. Although hemoglobin (Hb, and associated red blood cells) and white blood cells, and possibly interleukin-6 immunoreactive responded in the expected manner, other parameters did not. Aspartate aminotransferase, alanine aminotransferase, and haptoglobin (Hp), did not increase in response to oiling or decreased during rehabilitation. Conversely, principle-component analysis identified values of alkaline phosphatase as responding to oil ingestion in river otters. Our results suggested that opposing processes were concurring in the oiled otters. Elevated production of Hp in response to tissue damage by hydrocarbons likely occurred at the same time with increased removal of Hp-Hb complex from the serum, producing an undetermined pattern in the secretion of Hp. Thus, the use of individual biomarkers as indicators of exposure to pollutants may lead to erroneous conclusions because interactions in vivo can be complicated and act in opposite directions. Additionally, the biomarkers used in investigating effects of oiling on live animals usually are related to the heme molecule. Because of the opposing processes that may occur within an animal, data from a suite of heme-related biomarkers may produce results that are difficult to interpret. Therefore, we advocate the exploration and development of other biomarkers that will be independent from the heme cycle and provide additional information to the effect of oiling on live mammals.

Alaska↗

Natural exposure of coastal river otters to mercury: relation to age, diet, and survival.

We evaluated effects of location (i.e., Jackpot Bay, a naturally contaminated site, and Herring Bay, reference site), diet as determined by stable isotopes, and age on mercury concentrations in individual river otters (Lontra canadensis) from Prince William Sound, Alaska, USA. We also investigated the effects of mercury accumulation on survival of river otters from these two locations. Our results indicated that mercury concentrations in fishes from Jackpot Bay were significantly higher than those in fishes from Herring Bay and those in pelagic fishes. In addition, a predominant intertidal fish diet in both areas influenced the accumulation of mercury concentrations in otters. Concentrations of mercury in fur of river otters from Jackpot Bay were significantly higher than those of animals from Herring Bay. Nonetheless, we did not detect significant differences in survival between otters inhabiting the two areas, suggesting that this natural contamination was not high enough to impair survival. Our ability to investigate the effects of various factors such as location, diet composition, and age on mercury accumulation and subsequent survival of individuals offers an example for a link between individual-based captive studies and population-level field investigations.

Age Factors↗

Ingestion of crude oil: effects on digesta retention times and nutrient uptake in captive river otters.

Studies following the Exxon Valdez oil spill in Prince William Sound, Alaska indicated that river otters (Lontra canadensis) from oiled regions displayed symptoms of degraded health, including reduced body weight. We examined the fate of ingested oil in the digestive tract and its effects on gut function in captive river otters. Fifteen wild-caught males were assigned to three groups, two of which were given weathered crude oil in food (i.e., control, 5 ppm day(-1), and 50 ppm day(-1)) under controlled conditions at the Alaska Sealife Center. Using glass beads as non-specific digesta markers and stable isotope analysis, we determined the effects of ingested oil on retention time and nutrient uptake. Our data indicated that oil ingestion reduced marker retention time when we controlled for activity and meal size. Fecal isotope ratios suggested that absorption of lipids in the oiled otters might have been affected by reduced retention time of food. In addition, a dilution model indicated that as much as 80% of ingested oil was not absorbed in high-dose animals. Thus, while the ingestion of large quantities of weathered crude oil appears to reduce absorption of oil hydrocarbons and may alleviate systemic effects, it may concurrently affect body condition by impacting digestive function.

Alaska↗

Hollow waveguide for mid and thermal infrared radiation.

OBJECTIVE: A novel type of flexible hollow waveguide that facilitates delivery of infrared radiation from source to treatment site, and made of polyimide tubes, was developed. SUMMARY BACKGROUND DATA: Polyimide tubes with flat internal wall and optimal conditions of deposition of guiding metal and dielectric layers were used to obtain low losses of radiation and high quality of beam shape. METHODS: Etching of the internal wall of polyimide tubes, high reflective metal (silver) layers and suitable dielectric layers (index of refraction and thickness) were deposited as guiding elements to obtain a waveguide suitable for infrared transmission. RESULTS: Polyimide waveguides of very low attenuation (transmission of approximately 95% through 1 meter length) beam profile of variable shape as a function of bending radius and type of tbe, large delivered radiation power (more than 25 Watts), constant delivered power as a function of time (during more than 250 seconds), and very low divergence of the delivered beam (angle of divergence less than 1 degree), were obtained. The polyimide waveguides also are very flexible and may be bent to a radius of bending less than 5 cm. The polyimide plastic hollow waveguide is suitable for medical applications (chemical and physical stable and nontoxic). CONCLUSIONS: The optical and mechanical parameters correspond with those requested for applications in medicine for infrared laser treatments or radiometric measurements (non-contact thermometry). Waveguides for applications in surgery are under preparation.

Carbon Dioxide↗

Prolactin and luteinizing hormone-releasing hormone receptors in human benign prostatic hyperplasia and prostate cancer.

Using a sensitive micromethod for the determination of prolactin (PRL) binding sites based on 125I-human PRL ligand, PRL receptor levels in specimens of benign prostatic hyperplasia (BPH) and human prostate cancer were estimated by the one-point assay system. Ten of 19 BPH specimens (53%), showed significant PRL binding, four being in the 9-12 fmol/mg range. All ten of these cases had an histological diagnosis of nodular glandular hyperplasia. Of ten adenocarcinomas examined, four samples (40%) exhibited positive PRL binding, the highest receptor levels being 10.2 fmol/mg protein. To characterize the receptors from BPH membranes, samples were then separately pooled according to the results obtained in one-point assays. In the PRL-negative pool no displacement could be detected. In the PRL-positive pool, the Scatchard analysis revealed one class of receptors with an average affinity Kd = 1.1 X 10(-9) M and capacity Bmax = 287 fmol/mg protein. In the prostate cancer specimens, luteinizing hormone-releasing hormone receptors with a high affinity and a low capacity were also found. The results indicate the presence of prolactin receptors in prostate cancer and in BPH. The clinical implications of such findings are not clear, but it is possible that a certain proportion of BPH and prostate cancers might be in part PRL dependent. Further studies are necessary to ascertain this hypothesis in an attempt to improve the treatment of BPH and prostate cancer.

Gonadotropin-Releasing Hormone↗

Receptors for prolactin, somatostatin, and luteinizing hormone-releasing hormone in experimental prostate cancer after treatment with analogs of luteinizing hormone-releasing hormone and somatostatin.

Membrane receptors for luteinizing hormone-releasing hormone (LH-RH), somatostatin, and prolactin (PRL) were investigated in the Dunning R-3327H rat prostate adenocarcinoma specimens after in vivo treatment with microcapsules of the agonist [D-Trp6]LH-RH and the somatostatin analog RC-160. The LH-RH receptors showed a low-binding affinity (Kd = 54 nM) and high capacity (Bmax = 12.0 pmol/mg). Treatment with the [D-Trp6]LH-RH decreased the binding affinity (Kd = 0.52 microM). Specific somatostatin receptors, with Kd = 1.3 nM and Bmax = 543 fmol/mg, were also found. Treatment with [D-Trp6]LH-RH lowered Bmax to 44 fmol/mg, and administration of RC-160 reduced Kd to 30 nM. After the combined treatment with the two analogs, Kd and Bmax were decreased. Specific PRL receptors (Kd = 0.72 nM; Bmax = 161 fmol/mg) were also detected. Treatment with either analog reduced Bmax by 50%, but a much greater reduction of PRL binding capacity was revealed after in vitro dissociation of the bound endogenous PRL by MgCl2. The dramatic fall in the total number of PRL receptors after combination treatment with both analogs could be partially responsible for the decrease in the weight and volume of prostate tumors. The findings support the concept that analogs of LH-RH and somatostatin can inhibit tumors directly through their own respective receptors. One of several mechanisms of the antineoplastic activity of these analogs could be the elimination of tumor growth-promoting effect of PRL by the reduction of the total number of PRL receptors.

Adenocarcinoma↗

First trimester bleeding in clinical IVF pregnancies.

First trimester bleeding has been investigated in 72 pregnant women undergoing in-vitro fertilization and embryo transfer and was compared to 70 pregnant patients in whom ovulation was induced, in addition to 70 spontaneous pregnancies. Abortion rates did not differ significantly between the first two groups but were significantly higher in comparison to normal pregnancies. Furthermore, among IVF pregnancies that continued, a high incidence of first trimester bleeding occurred (P less than 0.01). This complication was mainly related to luteal insufficiency and multiple pregnancies, whereas hyperstimulation was the major risk factor for bleeding in pregnancies arising from HMG-induced ovulation. Other currently unknown, aetiological factors for first trimester bleeding in IVF pregnancies remain to be investigated.

17 alpha-Hydroxyprogesterone Caproate↗

Induction of ovulation with D-Trp6-LHRH combined with purified FSH in patients with polycystic ovarian disease.

Seventeen patients with polycystic ovarian disease (PCOD) and evidence of mild or severe ovarian hyperstimulation syndrome (OHSS) during therapy with CC/hCG, FSH/hCG or hMG/hCG were treated with D-Trp6-LHRH until medical gonadectomy was attained. Under the suppressive therapy with the GnRH agonist (GnRHa) ovulation was induced with FSH/hCG. In 15 out of 17 patients, ovulatory cycles were obtained with this new modality of treatment. Seven patients conceived (3 viable pregnancies and 4 early abortions) after the 1st treatment cycle. Fourteen of the 17 patients demonstrated symptoms of mild OHSS which did not require hospitalization. Only 1 patient developed severe OHSS after the combined treatment. Our results suggest that therapy with GnRHa, especially in its delayed release formulation, is effective for the prevention of severe ovarian hyperstimulation in PCOD patients undergoing treatment with menotropins for the induction of ovulation.

Adult↗

Characterization of prolactin receptors and their distribution among American and Israeli women with breast cancer: implications for prediction of hormonal dependency and treatment.

A micro-method is reported for the determination and characterization of prolactin (PRL) receptors in human breast cancer specimens using either intact biopsy tissue or the pellet fraction remaining from biopsies previously processed for steroid hormone receptors. Labeled human PRL is used as the ligand. The specific PRL-binding of 307 human breast cancer specimens was evaluated by this micro-method. A significant level of specific PRL-binding (3-25 fmol per mg membrane protein) was detected in 41% of US breast cancer patients and 42% of Israeli patients. Scatchard analyses, performed on pooled membrane fractions with the highest specific PRL-binding revealed one class of receptors having a dissociation constant, Kd = 4.1 x 10(-9), and specific binding capacity, Bmax = 1.3 pmol per mg protein. These preparations were exposed to 3 M MgCl2, which dissociates the endogenous-bound PRL from the hormone-receptor complex and allows the characterization of the "total" PRL receptors. Two classes of receptors were then revealed. One class of receptors showed high affinity (Kd1 = 8.1 x 10(-10) M) and low capacity (Bmax1 = 335 fmol per mg protein), while the other possessed lower affinity (Kd2 = 8.2 x 10(-8) M), but a higher capacity (Bmax2 = 34.4 pmol per mg protein). Since PRL facilitates the growth of human breast cancer cell lines, these results indicate that a high proportion of human breast cancers may be PRL dependent. Routine determination of PRL receptors in biopsies of human breast cancer may permit the selection of a better treatment, since it is possible that the reduction in PRL levels could inhibit those tumors which are prolactin dependent.

Breast Neoplasms↗

Lack of relationship between the levels of prolactin receptors and steroid receptors in women with breast cancer.

The levels of prolactin receptors (PRL-R), based on a new micro-method, estrogen receptors (ER) and progesterone receptors (PG-R), were determined in 159 breast cancer specimens. Sixty-seven of 159 tumors (42%) had PRL-R levels of 20 fmol/mg protein or higher, and were regarded as PRL-R positive. In 60 of the 159 samples (38%), no PRL-R could be detected, and the remaining 32 samples (20%) were considered borderline. While a positive correlation was found between the presence of ER and PGR, no correlation was detected between PRL-R and any steroid receptors (r = -0.024 for ER vs PRL-R, 0.052 for PGR vs PRL-R and 0.002 for ER + PGR vs PRL-R). Furthermore, PRL-R in levels of 20 fmol/mg protein or higher were found in 35% of samples in which no steroid receptors were detected as well as in 38% and in 27% of samples which exhibited positive ER or PGR respectively (greater than or equal to 20 fmol/mg protein). On the other hand, in 47% of the samples possessing both ER and PGR, the PRL receptors could not be found. These results clearly demonstrate that in the human breast cancer, the presence of PRL-R is independent of the status of either ER or PGR. It is suggested that the measurement of PRL-R could serve as a chemical marker to guide a possible therapeutic use of PRL-suppressing drugs in women with breast cancer.

Adult↗

Micromethod for the determination of free and total prolactin receptors: measurement of receptor levels in normal and malignant mammary and prostate tissues.

A sensitive micromethod for the determination of free and total prolactin receptors in normal or malignant tissues has been developed. Positive and negative quality controls are incorporated in the procedure. Either whole tissue or the pellet fraction remaining from tissue that had undergone processing for estrogen receptors can be used. Crude microsomal and plasma membrane fractions obtained by homogenization and differential centrifugation are incubated with labeled prolactin in the presence or absence of increasing amounts of unlabeled hormone. The labeled ligand is prepared by a stoichiometric iodination procedure in which one atom of iodine-125 is incorporated into one molecule of the hormone, resulting in an intact labeled prolactin with a high specific activity of 170-186 muCi/micrograms (1 Ci = 37 GBq). Human prolactin labeled by this procedure has much greater specific binding capacity to various rat tissues than does iodinated rat prolactin. This technique permits an accurate measurement of prolactin receptors in as little as 50 micrograms of membrane protein. Highest levels of free and total prolactin receptors were found in the liver of 60-day-old female rats that served as a positive control. Liver of immature 21-day-old male rats, devoid of prolactin receptors, was used as a negative control. The amount of detectable free receptors was dependent on the level of circulating plasma prolactin. In 3-day postpartum lactating rats with high prolactin levels in plasma, all prolactin receptors in the mammary glands were found to be occupied, and no free receptors could be detected. When these receptors were desaturated from the endogenous prolactin by exposure to 3 M MgCl2, one class of receptors in a high quantity (1.75 nmol/mg of protein) and with a moderate affinity (Kd = 6.41 X 10(-9) M) was detected. A similar type of receptor was found in the mammary glands of rats at midpregnancy and of cycling adult female rats. In malignant rat mammary tissue, however, fewer receptors (27 pmol/mg of protein) but with a very high affinity (Kd = 6.8 X 10(-14) M) were detected. Normal ventral and dorsolateral rat prostate contained two classes of prolactin receptors (Kd = 3.46 X 10(-10) M and 1.93 X 10(-8) M). In the cancerous rat prostate, however, only one of these two classes of receptors was detected, and the number was smaller.

Animals↗

Hematoma of the umbilical cord with acute antepartum fetal distress. A case report.

In a case of spontaneous hematoma of the umbilical cord, no pathologic lesion was found in the umbilical blood vessels. However, an extremely short cord (14 cm) may have contributed to the vessel rupture. A prolonged deceleration discovered during a routine nonstress test led to emergency cesarean section, with delivery of a healthy neonate.

Cesarean Section↗

Sulpiride-induced hyperprolactinemia and impotence in male psychiatric outpatients.

The relationship between erectile dysfunction and sulpiride stimulatory effect on prolactin secretion was studied in 13 married male psychiatric outpatients. The patients population was comprised of 2 groups: patients with anxiety disorders resistant to minor tranquilizers who were treated with sulpiride up to 200 mg/day, and schizophrenic patients treated with sulpiride 600 mg/day. All the patients were maintained on maximal dose for a period of 3 weeks. Sexual function and blood prolactin levels were monitored once weekly. The patients who developed impotence were maintained on higher doses of sulpiride and exhibited higher prolactin levels in comparison to the potent patients. Restoration of potency was observed after reduction or discontinuation of sulpiride treatment. It is concluded that sulpiride induced impotence is associated with hyperprolactinemia.

Adult↗

Prolactin response to the cold pressor test in patients with panic attacks.

Recent advances in psychiatric nosology have provided a clearer clinical description of panic disorder and agoraphobia with panic attacks. This clinical improvement has yet to result in a better understanding of the basic mechanisms involved in these conditions. The present study compares the effects of the cold pressor test on blood pressure changes and prolactin levels in patients with panic disorder and agoraphobia with panic attacks to its effects in normal controls. Because the effects of the cold pressor test were similar in patients and normal controls, it appears that alpha-adrenergic function is normal in the patient group. The results also suggest that prolactin hypersecretion does not occur in pathological anxiety states.

Adult↗