Properties of fibres,endplates and acetylcholine receptors in the diaphragm,masseter, laryngeal,abdominal and limb muscles in the goat

Purpose

Although differences in fibre composition, fibre size or acetylcholine receptor (AChR) density between muscles have often been proposed to explain the unequal sensitivities of muscles to muscle relaxant drugs, it is not clear whether or how these parameters differ among muscles or are related to one another. In this study, several muscles were examined to determine the composition and cross-sectional area (CSA) of types I and II fibres, the surface area of their motor endplates (ESA), and their AChR density.

Methods

Biopsies from the thyroarytenoideus, cricoarytenoideus dorsalis, masseter, diaphragm, transversus abdominis, rectus abdominis, gastrocnemius and soleus muscles of goats were processed by muscle histochemistry and morphometry and the ESA:CSA ratio was computed. The number and density of AChRs per endplate were estimated by¹²⁵I-α-bungarotoxin binding studies.

Results

The mean type 1 fibre composition (range: 0–100%), fibre diameter (28–50 μm) and the ESA:CSA ratio (0.27–1.01) differed among muscles (P = 0.0001), but there were no significant differences (P > 0.05) in the mean endplate size (577–725 μm²), AChR number (6.6?14.5 × 10⁶) or AChR density (8,900–22,300 μm^?2) probably because of marked individual variations. Fibre size increased and the ESA:CSA ratio decreased in the order laryngeal, diaphragm, jaw, limb and abdominal muscles.

Conclusion

It is concluded that between muscles fibre size varies more than endplate size or AChR number.     

Diffusion of information about genetic risk within families

Recent developments in genetics are likely to exacerbate the ethical issues in clinical practice, especially with regard to privacy and disclosure of genetic information. To evaluate the behaviour of patients with respect to transmitting carrier information, we undertook a survey of 283 families with a balanced chromosomal rearrangement as a model. In these families, 1816 relatives were considered at risk and 806 of them were karyotyped (44.4%). The percentage of karyotypes performed is significantly related to the number of living children of the index couple, the reason for referral, the nature of the anomaly, the training of the counsellor and the age of the index case. This study shows the limits of the screening of at risk individuals within families, based on the willingness of the patients, and addresses practical and ethical issues around family disclosure in medical genetics.     

Leucoéncephalopathie multifocale progressive

Summary A young woman presented a mixed congenital and familial immunodeficiency syndrome consisting in an absence of IgA and lowered levels of IgG and IgM, with a defect in cellular immunity. She had a mild malabsorption syndrome with slight alterations of the jejunal mucosa. Non-caseating tuberculoid granulomata were found in skin lesions, in lymph nodes and in the spleen. At age 27 the patient died of a neurological disease of 4 months duration. Autopsy revealed a very widespread demyelinating process involving mainly the right cerebellar hemisphere but also most of the pons and left cerebellum, with the typical morphologic characters of PML. In the hemispheres lesions were limited to microscopical microglial nodules with discrete demyelination. A review of 86 published cases of PML revealed 9 other cases in which lesions showed a strong predilection for the subtentorial territories. This sampling allows for the assumption that some 11% of the cases of PML have this particular lesion distribution. Other pertinent features of this case are briefly discussed.

     

THIP inhibits feeding behavior in fasted rats

The effects of 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol (THIP) were compared with those of d-amphetamine and GABA in fasted rats. Intravenously-administered THIP produced a dose-dependent decrease in food consumption (ED₅₀1.5 mg/kg) by an action that was not reversed by prior subcutaneous or simultaneous intravenous (IV) injection of bicuculline. d-Amphetamine-SO₄ also produced a decrease in food consumption in this model (ED₅₀0.2 mg/kg, IV). Unlike THIP, GABA (in doses up to 100 mg/kg, IV) did not produce a marked anorexigenic effect. These results provide further evidence that THIP can penetrate the blood-brain barrier, and that central GABA-ergic systems are involved in controlling food intake.     

Ultrasonographic study of the effect of different miotics on the eye components.

The effect of topical instillations of carbachol 3%, pilocarpine 2%, aceclidine 2%, aceclidine 2%-adrenaline 1%, and of the Ocusert delivery system was determined and compared in 151 eyes. The depth of the anterior chamber, the thickness and the position of the lens, the length of the vitreous and the refraction were studied. Aceclidine has negligible side effects on the ocular components (maximal change of the anterior chamber 0.20 mm; maximal change of the lens thickness 0.14 mm; maximal myopisation: -1.5 delta. Carbachol has the strongest side effects (maximal change of the anterior chamber 0.80 mm; maximal change of the lens thickness 0.80 mm; maximal myopisation -11.50 delta). Carbachol and pilocarpine may cause an important forward displacement of the lens with the risk of an angle-closure glaucoma in an eye with shallow anterior chamber.     

Spray-dried redispersible oil-in-water emulsion to improve oral bioavailability of poorly soluble drugs.

A physically stabilized dry emulsion dosage form reforming the original emulsion after rehydration was developed by spray-drying a liquid oil-in-water emulsion containing maltodextrin as carrier and sodium caseinate as emulsifying agent. Several oil:water as well as maltodextrin:water ratios were tested, the homogenization and spray-drying processes and the reconstitution properties were investigated and an optimum formulation was selected for poorly soluble drug incorporation, having an identical oil:water and carrier:water ratio of 10% (w/w) and a load of solid material of 20% (w/w). Lipophilic 5-phenyl-1,2-dithiole-3-thione (5-PDTT) was selected as a model drug. 5-PDTT release from the solid state emulsion was studied using an in vitro two-phase stirred model and the relative bioavailability of 5-PDTT in the dry emulsion was obtained in the rabbit after oral administration of the reconstituted emulsion, compared to a 5-PDTT-sulfobutyl ether 7 beta-cyclodextrin complex in solution. Incorporation of 5-PDTT in the oil phase neither affects the surface morphology of the powder nor the reconstitution, the droplet size or the drug releasing properties and, furthermore, allows a 3-fold improvement of 5-PDTT relative bioavailability in rabbit after oral administration. These results indicate that dry emulsions may be considered as relevant dosage forms to improve bioavailability of poorly absorbable lipophilic drugs.     

SSR181507, a dopamine D(2) receptor antagonist and 5-HT(1A) receptor agonist. I: Neurochemical and electrophysiological profile.

SSR181507 ((3-exo)-8-benzoyl-N-[[(2S)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl]methyl]-8-azabicyclo[3.2.1]octane-3-methanamine monohydrochloride) is a novel tropanemethanamine benzodioxane derivative that possesses high and selective affinities for D2-like and 5-HT(1A) receptors (K(I)=0.8, 0.2, and 0.2 nM for human D(2), D(3), and 5-HT(1A), respectively). In vivo, SSR181507 inhibited [(3)H]raclopride binding to D(2) receptors in the rat (ID(50)=0.9 and 1 mg/kg, i.p. in limbic system and striatum, respectively). It displayed D(2) antagonist and 5-HT(1A) agonist properties in the same concentration range in vitro (IC(50)=5.3 nM and EC(50)=2.3 nM, respectively, in the GTPgammaS model) and in the same dose range in vivo (ED(50)=1.6 and 0.7 mg/kg, i.p. on striatal DA and 5-HT synthesis, respectively, and 0.03-0.3 mg/kg, i.v. on dorsal raphe nucleus firing rate). It selectively enhanced Fos immunoreactivity in mesocorticolimbic areas as compared to the striatum. This regional selectivity was confirmed in electrophysiological studies where SSR181507, given acutely (0.1-3 mg/kg, i.p.) or chronically (3 mg/kg, i.p., o.d., 22 days), increased or decreased, respectively, the number of spontaneous active DA cells in the ventral tegmental area, but not in the substantia nigra. Moreover, SSR181507 increased both basal and phasic DA efflux (as assessed by microdialysis and electrochemistry) in the medial prefrontal cortex and nucleus accumbens, but not in the striatum. This study shows that the combination of D(2) receptor antagonism and 5-HT(1A) agonism, in the same dose range, confers on SSR181507 a unique neurochemical and electrophysiological profile and suggests the potential of this compound for the treatment of the main dimensions of schizophrenia.     

Pulmonary haemorrhage causing rapid death after Bothrops jararacussu snakebite: a case report.

A 36-year old woman was bitten on the left ankle by a Bothrops jararacussu, and died 45 min after the bite. At necropsy, there were local signs of envenoming with haemorrhage, thrombosis and necrosis of the subcutaneous and muscular tissue. Multiple fibrin and platelet thrombi were found in the microcirculation of the heart and lungs, suggesting the occurrence of disseminated intravascular coagulation. Pulmonary haemorrhage probably secondary to the action of haemorrhagins, consumption coagulopathy and disseminated intravascular coagulation was the immediate cause of death. Intravenous inoculation of the venom could have occurred in the present case, which would explain the rapid onset of coagulation disorders, haemorrhage and death.