Behavioral effects of alpha-MSH and MCH after central administration in the female rat

The behavioral effects of alpha-MSH, MCH, and alpha-MSH + MCH were investigated in the ventromedial nucleus (VMN) and medial preoptic area (MPOA) (bilateral, 100 ng in 0.5 microliter). Infusion of alpha-MSH into the VMN increased aggressive behavior; in the MPOA it reduced exploration and increased anxiety. In both areas it stimulated sexual behavior. MCH also stimulated sexual behavior in the MPOA and VMN and had an anxiogenic effect in the MPOA. The effect of alpha-MSH on aggression and exploration was antagonized by MCH. When given together, the two peptides were mutually antagonistic on anxiety. This study indicates that MCH has central nervous system effects and may be a partial alpha-MSH agonist.     

Evaluation of erectile dysfunction and sleep-related erections

Significant advances in this past decade have improved our understanding of erectile physiology. A variety of tests are available for diagnosing impotence. SRE testing provides objective physiological information that is useful for indexing erectile capability and formulating a rational treatment plan. As such, SRE testing is a powerful noninvasive tool for assessing dysfunction. Nonetheless, in making a final diagnosis, the skillful clinician relies on more than one assessment parameter and on clinical acumen.     

Use of capillary electrophoresis in the characterization of sulfonated metallophthalocyanines: a comparative evaluation of purification procedures following synthesis by the condensation method

Capillary electrophoresis has been presented as a resourceful technique for monitoring the purity of synthetic metallophthalocyanines and evaluating comparatively purification procedures. In this study, the tetrasulfonated cobalt(II) phthalocyanine was synthesized by the condensation method and submitted to several purification procedures such as continuous Soxhlet extraction with ethanol and dioxane, percolation through a gel-filled chromatographic column, and salting-out precipitation in acid medium followed by washing with alkaline solution. The efficiency of each procedure, or combined procedures, was then evaluated by capillary electrophoresis in citrate buffer solution under constant voltage conditions and direct UV-VIS detection at 630 nm and 260 nm. The inorganic anion and cation composition of the purified fractions was also investigated by indirect UV analysis in chromate/cetyltrimethylammonium bromide (CTAB) and imidazole/hydroxyisobutyric acid (HIBA) electrolyte systems, at 254 nm and 214 nm, respectively. The electropherograms obtained at 630 nm showed a high-intensity peak surrounded by satellite peaks of small intensity with migration time of approximately 5-6 min. This profile is indicative of the formation of positional isomers under the synthesis conditions. The electropherograms obtained at 260 nm were useful to monitor contaminants, such as reaction by-products or unreacted starting materials. The salting-out precipitation of the crude product led to a good-quality product with 80% purity (elemental analysis based on nitrogen content), which is comparable to the purity of commercially available tetrasulfonated derivatives. Both UV and infrared (IR) spectra of the purified product resemble that of standards. The capillary electrophoresis ion analysis of the treated product revealed the presence of sodium carbonate as the major contaminant. The combined treatment of salting-out precipitation followed by percolation in a Sephadex column (Pharmacia, S?o Paulo, Brazil) was successful for the removal of carbonate ion. However, the percolation procedure seemed to cause minor demetallation of the macrocycle ring, as confirmed by the presence of free cobalt(II) in the electropherogram of the column eluted fraction.     

Congenital superficial angiomyxoma

Superficial angiomyxomas are rare, benign, dermal and subcutaneous tumours. We describe a 12-year-old girl who presented with a nodular swelling in the midline of her scalp that had been present since birth. Histological examination revealed an ill-defined myxoid lesion within the dermis, comprising spindle cells, blood vessels and occasional multi-nucleate giant cells. Immunohistochemical staining was negative for S-100, cytokeratin and smooth muscle actin, but focally positive for CD34. Our patient is unusual in that the angiomyxoma was present at birth, which has not previously been described. The importance of screening patients with cutaneous myxomas for cardiac lesions is discussed.     

The central cholinergic stimulation in sinoaortic denervation. Effect of intracerebroventricular administration of cholinomimetic agents

Preclinical trials of intravenously administered 4-Aminopyridine (4-AP) have demonstrated transient improvements in neurological function in patients with longstanding spinal cord injury (SCI). The present report describes three patients with SCI who responded favourably in preclinical trials and who were subsequently administered oral (capsule) 4-AP (10 mg b.i.d. or t.i.d.) over a 4 month interval. The three patients (two male: 1 female) all had incomplete tetraplegia (ASIA levels C and D) with the neurological level of the lesion between C5-C7. Following the administration of 4-AP the patients demonstrated marked and sustained reductions in upper (n = 1) or lower extremity (n = 2) spasticity. Other clinical benefits of 4-AP were reduced pain (n = 1), restored muscle strength (n = 3), improved sensation (n = 2), voluntary control of bowel function (n = 1), and sustained penile tumescence (n = 2). The patients exhibited improved hand function (n = 1), enhanced mobility in transfers and gait (n = 2), with improved energy and endurance. Only trivial side effects (transient light-headedness) were observed. In one case, the enhanced neurological function allowed the patient to stand with support for the first time post injury (16 years). The time course of therapeutic response to the initial dose matched the pharmacokinetic elimination profile derived from serum and urine analysis. There was no evidence of renal or hepatic toxicity with prolonged use. These results indicate a therapeutic benefit of oral 4-Aminopyridine in the management of various neurological deficits in a select group of SCI patients.     

ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine]: I. A potent and selective cholinergic channel modulator with neuroprotective properties

Lactate dehydrogenase from the malarial parasite Plasmodium falciparum has many amino acid residues that are unique compared to any other known lactate dehydrogenase. This includes residues that define the substrate and cofactor binding sites. Nevertheless, parasite lactate dehydrogenase exhibits high specificity for pyruvic acid, even more restricted than the specificity of human lactate dehydrogenases M4 and H4. Parasite lactate dehydrogenase exhibits high catalytic efficiency in the reduction of pyruvate, kcat/Km = 9.0 x 10(8) min(-1) M(-1). Parasite lactate dehydrogenase also exhibits similar cofactor specificity to the human isoforms in the oxidation of L-lactate with NAD+ and with a series of NAD+ analogs, suggesting a similar cofactor binding environment in spite of the numerous amino acid differences. Parasite lactate dehydrogenase exhibits an enhanced kcat with the analog 3-acetylpyridine adenine dinucleotide (APAD+) whereas the human isoforms exhibit a lower kcat. This differential response to APAD+ provides the kinetic basis for the enzyme-based detection of malarial parasites. A series of inhibitors structurally related to the natural product gossypol were shown to be competitive inhibitors of the binding of NADH. Slight changes in structure produced marked changes in selectivity of inhibition of lactate dehydrogenase. 7-p-Trifluoromethylbenzyl-8-deoxyhemigossylic acid inhibited parasite lactate dehydrogenase, Ki = 0.2 microM, which was 65- and 400-fold tighter binding compared to the M4 and H4 isoforms of human lactate dehydrogenase. The results suggest that the cofactor site of parasite lactate dehydrogenase may be a potential target for structure-based drug design.