Combined Drug Treatment of Obesity

Pharmacological treatment of obesity has been neglected as a viable therapeutic option for many years. Recent long term studies with combinations of obesity drugs gives promise that drugs may play a role in weight maintenance, which classically has been the most difficult aspect of treating obesity. Currently available obesity drugs include centrally acting adrenergic agents and serotonin agonists. Drugs still in development include a lipase inhibitor that produces fat malabsorption, a combined adrenergic-serotonergic reuptake inhibitor, various gut-central nervous system peptides, and a number of beta-3 agonists. Any of these obesity drugs given alone produces modest weight loss, and for most, weight loss continues for as long as medication is given. The most successful drug regimens to date are combinations of phentermine and fenfluramine or of ephedrine, caffeine, and/or aspirin. The former combination produces reduction in body weight and complications of obesity for 2 to almost 4 years in clinical trials to date. More research is needed to document long term efficacy and particularly the long term safety of these and other combinations.     

The use and abuse of pollinators by fungi

Some fungi use flower-visiting insects to facilitate sexual reproduction or to disperse spores. These fungi have evolved elaborate techniques, such as floral mimicry and the invasion of extant flower parts, for attracting 'pollinators'. Recent research shows that fungal exploitation of pollinators has the potential to affect floral evolution, pollination ecology, plant life history traits, as well as disease-transmission dynamics and fungal evolution.     

Hormonotoxins: the role of positive charge of lysine residue on the immunological,biological and cytotoxic properties of ovine lutropin-S-S-gelonin conjugates

Since the positive charge on the lysine residues plays an important role in the receptor recognition ability of oLH, the hormonotoxin has been synthesised with the use of 2-iminothiolane HC1 (2IT) and N-Succinimidyl-3-(2-pyridyldithio)-propionate (SPDP). The oLH activated with 2IT (oLH-10) was then mixed with SPDP activated gelonin (gelonin-30) in order to obtain a oLH-S-S-gelonin hormonotoxin. The conjugation mixture containing hormonotoxin was purified by gel-filtration chromatography according to the molecular weight and a complete physico-chemical, immunochemical and biochemical analysis were performed. The linkage occured through the -NH₂ groups of -subunit of oLH as judged from RP-HPLC analysis. A 11 (oLH:gelonin) molar ratio was obtained when determined with the use of several techniques. The hormonotoxins retained substantial receptor binding, steroidogenic activity and immunoreactivity. The competitive displacement analysis indicate that the binding occurs via the hormone part leaving the gelonin free which was probed with the gelonin antibodies. The presently described (C150A-02, C160A-02 and C170A-02) hormonotoxins exhibited higher receptor binding and toxicity to the target cells than the hormonotoxins prepared with the use of SPDP only. Therefore it is concluded that higher receptor binding and cytotoxicity may be due to the retention of positive charge on the lysine residues of oLH which was preserved during the conjugation process.Abbreviations BSA Bovine Serum Albumin - CMC Carboxy methyl Cellulose - DTT Dithiothreitol - DMEM Dulbeco's Modified Eagle's Medium - DTNB Ellman's reagent [5,5-dithio-bis-(2-nitrobenzoic acid)] - EDTA Ethylenediaminetetraacetic acid - FPLC Fast Protein Liquid Chromatography - FCA Freund's Complete Adjuvant - FCS Fetal Calf Serum - Gelonin-30 Gelonin modified by SPDP - GnRH Gonadotropin-Releasing Hormone - Gelonin-SPDP SPDP modified derivative of gelonin - HEPES (N-[2-hydroxyethyl] piperazine-N-[-2-ethanesulphonic acid]) - IFA Incomplete Freund's Adjuvant - 2IT 2-Iminothiolane - IODOGEN 1,3,4,6-tetrachloro 3,6-diphenylglycouril - oLH Ovine Luteinizing Hormone - oLH-SPDP SPDP modified derivative of oLH - oLH-10 oLH modified by 2IT - oLH2IT Molar ratio of oLH and 2IT - PDP 2-Pyridyl-dithiopropionate - PAP Pokeweed Antiviral Protein - RIP Ribosome Inactivating Protein - RP-HPLC Reverse-Phase High Performance Liquid Chromatography - RPMI Roswell Park Memorial Institute - RIA Radioimmunoassay - RRA Radioreceptor Assay - SPDP N-Succinimidyl-3(2-pyridyldithio)propionate - SDS-PAGE Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis - TCA Trichloroacetic acid - TFA Trifluroacetic acid     

Hand dominance and bilateral asymmetry in the structure of the second metacarpal

Bilateral asymmetry in the structure of the second metacarpal was examined in relation to functional hand dominance in a large, clinically nonselected, healthy population sample from the Baltimore Longitudinal Study of Aging. Bilateral bone measurements were made from anteroposterior hand radiographs of a total of 992 individuals, 609 males and 383 females, with an age range of 19–94 years. Hand dominance was determined on the basis of personal impression. Total width and medullary width at the midshaft of the second metacarpal were measured to 0.05 mm using a Helios caliper. These two measurements were used to derive cortical thickness, cortical bone area, periosteal (total) area, medullary area, percent cortical area, and the second moment of area in the mediolateral plane. In both right and left-handed individuals, statistically significant side differences were found in the calculated bone areas and the second moment of area, with the dominant hand being larger. Cortical thickness did not show significant side-related differences for either handedness. These results show that functional handedness leads to periosteal and endosteal expansion of the second metacarpal cortex on the dominant side, increasing bone strength without increasing cortical thickness. This is the first time this pattern of asymmetry has been reported in left-handers as well as right-handers. Our results argue for the primacy of environmental (mechanical) effects in determining bilateral asymmetry of limb bone structural properties. © 1994 Wiley-Liss, Inc.     

Mating system parameters and population genetic structure in pioneer populations of Prosopis velutina (Leguminosae)

This study describes the genetic structure and provides estimates of mating system parameters in three natural populations of Prosopis velutina Woot. in southeastern Arizona. F statistics derived from isozyme data revealed the presence of both interpopulation and intrapopulation genetic differentiation. This population structure is discussed in relation to the ecological history of these populations that invaded the grasslands sites from adjacent riparian areas within the last 90 years, and possible modes of seed dispersal. The multilocus estimation program MLT of Ritland (Journal of Heredity 8: 235–237, 1990) was used to provide estimates of t_s, t_m, and the fixation index (F) of the maternal parents. Average estimates of t_s ranged from 0.591 to 0.912. Estimates of t_m ranged from 0.609 to 1.004, and averaged 0.758. The difference between t_m and t_s, which provides a measure of biparental inbreeding, averaged 0.058. This last result, together with significant heterogeneity found in pollen allele frequencies, suggests that a family structure has developed in the populations. A negative F value for one of the populations suggests selection against homozygotes between the seedling stage and maturity.     

Effects of Methane Metabolism on Nitrification and Nitrous Oxide Production in Polluted Freshwater Sediment

We report the effect of CH₄ and of CH₄ oxidation on nitrification in freshwater sediment from Hamilton Harbour, Ontario, Canada, a highly polluted ecosystem. Aerobic slurry experiments showed a high potential for aerobic N₂O production in some sites. It was suppressed by C₂H₂, correlated to NO₃^- production, and stimulated by NH₄⁺ concentration, supporting the hypothesis of a nitrification-dependent source for this N₂O production. Diluted sediment slurries supplemented with CH₄ (1 to 24 μM) showed earlier and enhanced nitrification and N₂O production compared with unsupplemented slurries (≤1 μM CH₄). This suggests that nitrification by methanotrophs may be significant in freshwater sediment under certain conditions. Suppression of nitrification was observed at CH₄ concentrations of 84 μM and greater, possibly through competition for O₂ between methanotrophs and NH₄⁺ -oxidizing bacteria and/or competition for mineral N between these two groups of organisms. In Hamilton Harbour sediment, the very high CH₄ concentrations (1.02 to 6.83 mM) which exist would probably suppress nitrification and favor NH₄⁺ accumulation in the pore water. Indeed, NH₄⁺ concentrations in Hamilton Harbour sediment are higher than those found in other lakes. We conclude that the impact of CH₄ metabolism on N cycling processes in freshwater ecosystems should be given more attention.     

Sublethal malathion induced changes in the ovary of an air-breathing fish,Heteropneustes fossilis: a histological study

This paper describes effects of a sublethal (1.2 mg 1^–1) organophosphate, malathion, on the ovary of an air breathing catfish, Heteropneustes fossilis. The study focuses on microscopic changes that occur on ovigerous lamellae, oocytes at different stages of development and the nucleus of the immature oocyte. Also, change in estrogen levels in blood serum is investigated. Clumping of cytoplasm appears after 24 h of exposure to malathion. Clumping intensified after 48 h. Degeneration in the follicular cells was also observed. After 72 h exposure the number of nucleoli increased, nuclear materials shrunk, oocytes became adhered. With 96 h of exposure, nuclear materials of all the oocytes shrunk to a smaller clump. The oocytes fused together, and follicular epithelium became loose and ruptured. A few atretic oocytes were visible. Radioimmunoassay of the estrogen level in blood serum after 72 h of exposure of malathion showed a reduction in the level. This study showed that the histopathological condition of the gonad is reflected in malfunctioning of the endocrine system and hormonal disbalance.     

Pollen mitosis in the slipper orchid Cypripedium fasciculatum

Pollen mitosis in the slipper orchid Cypripedium fasciculatum was studied using correlated methods of immunofluorescence and transmission electron microscopy. Unlike the more highly evolved orchids, the cypripedioid orchids shed pollen as monosulcate monads. Prior to pollen mitosis, the microspore nucleus migrates to a proximal position opposite the aperture, as is typical of monocotyledons. There is no distinct generative pole microtubule system (GPMS) like that recently reported in development of pollen polarity in the vandoid moth orchid Phalaenopsis. Instead, microtubules in early prophase are concentrated around the nucleus and extend into the cytoplasm toward the future generative pole. Once the nucleus has migrated to the continuous surface opposite the aperture, microtubules surround the nucleus evenly and show no tendency to be more concentrated in the generative domain. The mitotic spindle, which develops from the perinuclear microtubules, is asymmetrically placed in the microspore and is cone-shaped. The generative pole is broad and closely appressed to the continuous spore surface, while the vegetative pole is pointed and located in the interior of the microspore. As the chromosomes move poleward, microtubules proliferate in the interzone and a phragmoplast develops. The phragmoplast expands in a hemispherical path beyond the interzone following an array of microtubules that radiates from the generative nucleus. Data from this study indicate that evolution of pollen in orchids includes a shift in location of the generative cell from proximal to distal and the evolution of a GPMS, in addition in the well-known trend toward increased pollen aggregation and loss of exine.