Muscarinic modulation of endogenous noradrenaline release from adrenergic terminals in the guinea-pig colon

1 The present study examined the role of muscarinic receptors in the modulation of noradrenaline (NA) release in the guinea-pig isolated distal colon. The spontaneous endogenous NA overflow assayed by HPLC-ED was taken as an index of NA release from enteric noradrenergic nerve terminals. 2 Physostigmine (10 μm ) significantly enhanced spontaneous endogenous NA overflow. Hyoscine (muscarinic antagonist), (R)-(-)-trihexyphenidyl and telenzepine (M₁-selective antagonists), and 11[[2-[(diethylamino)methyl]-1-piperydil]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX 116, M₂-selective antagonist) inhibited NA overflow in a concentration dependent manner, with the following EC₅₀ values: 131.74 (18.19–953.96), 101.62 (58.83–175.60), 150 (60–330), 30 (5–170) nm , respectively. 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M₁- and M₃- selective antagonist) had no significant effect up to 100 μm . 3 The muscarinic agonist oxotremorine inhibited NA overflow in a concentration dependent manner, with an EC₅₀ value of 0.67 (0.30–1.51) μm . The response to oxotremorine was inhibited by muscarinic antagonists with the following order of potency: hyoscine = (R)-(-)-trihexyphenidyl = telenzepine > 4-DAMP >> AF-DX 116. 4 In the presence of 3 μm tetrodotoxin (TTX), the effect of oxotremorine and 4-DAMP was unchanged, while hyoscine, (R)-(-)-trihexyphenidyl, telenzepine and AF-DX 116, instead of inhibiting, significantly enhanced NA overflow. 5 The present results indicate that, in the guinea-pig colon, endogenous acetylcholine sustains spontaneous NA release by activating muscarinic receptors possibly located on interneurones. In addition, inhibitory muscarinic receptors may exist on adrenergic terminals.     

Management of headache in emergency room

Neurological Sciences - Headache is one of the most common symptoms that leads patients to the emergency room (ER) and is often related to diseases requiring prompt diagnosis and immediate...     

Distribution of spermatogenesis in the testicles of azoospermic men: the presence or absence of spermatids in the testes of men with germinal failure [published erratum appears in Hum Reprod 1998 Mar;13(3):780]

The aim of the study was to determine whether a prior diagnostic testicle biopsy can predict success or failure of testicular sperm extraction (TESE) with intracytoplasmic sperm injection (ICSI) in patients with non-obstructive azoospermia caused by testicular failure, and what is the minimum threshold of sperm production in the testis which must be surpassed for spermatozoa to reach the ejaculate. Forty- five patients with non-obstructive azoospermia caused by testicular failure underwent diagnostic testicle biopsy prior to a planned future TESE-ICSI procedure. The diagnostic testicle biopsy was analysed quantitatively, and correlated with the quantitative findings of spermatogenesis in patients with normal spermatogenesis, as well as with the results of subsequent attempts at TESE-ICSI. Men with non- obstructive azoospermia caused by germinal failure had a mean of 0-6 mature spermatids/seminiferous tubule seen on a diagnostic testicle biopsy, compared to 17-35 mature spermatids/tubule in men with normal spermatogenesis and obstructive azoospermia. These findings were the same for all types of testicular failure whether Sertoli cell only, maturation arrest, cryptorchidism, or post-chemotherapy azoospermia. Twenty-two of 26 men with mature spermatids found in the prior testis biopsy had successful retrieval of spermatozoa for ICSI, 12 of their partners became pregnant, and are either ongoing or delivered. The study suggests that 4-6 mature spermatids/tubule must be present in the testis biopsy for any spermatozoa to reach the ejaculate. More than half of azoospermic patients with germinal failure have minute foci of spermatogenesis which are insufficient to produce spermatozoa in the ejaculate. Prior diagnostic testicle biopsy analysed quantitatively (for the presence of mature spermatids) can predict subsequent success or failure with TESE-ICSI. Incomplete testicular failure may involve a sparse multi-focal distribution of spermatogenesis throughout the entire testicle, rather than a regional distribution. Therefore, it is possible that massive testicular sampling from many different regions of the testes may not be necessary for successful TESE-ICSI.      

Adhesion inhibitory activity of β-lactoglobulin isolated from infant formulae

β-Lactoglobulin was isolated from infant formulae that were ultra high temperature (UHT) -treated, sterilized or spray-dried. The effect of the isolated β-lactoglobulin on SfaII-fimbriae-mediated adhesion of Escherichia coli to human ileostomy glycoproteins was studied in vitro. β-Lactoglobulin isolated from sterilized formulae was found to perform significantly less well than preparations from spray-dried formulae (p = 0:05). Great heterogeneity was observed in the adhesion inhibitory capacity of β-lactoglobulin isolated from UHT-treated formulae. Therefore, no significant difference was observed between UHT-treated and sterilized formulae or spray-dried formulae (p < 0:10). It can be hypothesized that β-lactoglobulin from spray-dried and some UHT-treated infant formulae may affect the colonization of mucous membranes by E. coli strains causing neonatal septicaemia and meningitis.     

Partial k-space reconstruction in single-shot diffusion-weighted echo-planar imaging.

Partial k-space sampling is frequently used in single-shot diffusion-weighted echo-planar imaging (DW-EPI) to reduce the TE and thereby improve the SNR. However, it increases the sensitivity of the technique to bulk rotational motion, which introduces a phase gradient across the tissue that shifts the echo in k-space. If the echo is displaced into the high spatial frequencies, conventional homodyne reconstruction fails, causing intensity oscillations across the image. Zero-padding, on the other hand, compromises the image resolution and may cause truncation artifacts. We present an adaptive version of the homodyne algorithm that detects the location of the echo in k-space and adjusts the center and width of the homodyne filters accordingly. The adaptive algorithm produces artifact-free images when the echo is shifted into the high positive k-space range, and reduces to the standard homodyne algorithm in the absence of bulk motion.     

Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch Type (HCHWA-D): I - A Review of Clinical, Radiologic and Genetic Aspects

Hereditary cerebral hemorrhage with amyloidosis - Dutch type (HCHWA-D) is an autosomal dominant disease caused by deposition of β-amyloid in the leptomeningeal arteries and cortical arterioles, in addition to preamyloid deposits and amyloid plaques in the brain parenchyma.
The disease is due to a point mutation at codon 693 of the amyloid precursor protein (βPP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke.
The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article     

Variations of the origin of the artery of the sinoatrial node in normal human hearts

Summary The artery of the sino-atrial node was studied in 100 normal human hearts after injection of each coronary artery with coloured gelatine containing a radiopaque substance. The hearts belonged to 69 males and 31 females, being 64 Caucasians and 36 non-Caucasians (Negroes and Mulattoes) whose age ranged from 7 to 80 years. Since the individuals had committed suicide or were victims of accidents, their hearts, after pathologists' evaluation, were considered normal. The sinoatrial node of the normal human heart is supplied by the right coronary artery more frequently (58%±4.9% of the cases) than by the left (42%±4.9). The right anterior medial atrial artery, originating from the right coronary at the level of the medial third of the right anterior quadrant of the atrial dome, is most frequently (50%±5) responsible for the blood supply of the sinoatrial node. Among the branches of the left coronary artery, the left anterior medial atrial artery, originating at the level of the medial third of the left. anterior quadrant of the atrial cupola, was the most frequent blood supplier (25%±4.3) of the sinoatrial node. The origin of the artery of the sinoatrial node from the proximal portion or trunk of the left coronary artery was less frequent (12%±3.2) than the origin from the circumflex artery (30%±4.5). Neither sex nor race influenced the variations of the origin of the sino-atrial node.

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Variations d'origine de l'artère du noeud sinu-atrial du coeur humain normal

Résumé L'a. du noeud sinu-atrial a été étudiée sur 100 coeurs humains normaux après injection de chaque a. coronaire à la gélatine colorée additionnée d'une substance radio-opaque. Les coeurs provenaient de 69 hommes et 31 femmes, 64 caucasiens et 36 non caucasiens (nègres et mulâtres) âgés de 7 à 80 ans. Ces sujets étant décédés par suicide ou des suites d'accidents, leurs coeurs ont été considérés comme normaux après examen anatomo-pathologique. Le noeud sinu-atrial du coeur humain est vascularisé par l'a. coronaire droite plus fréquemment (58 %±4,9) que par l'a. coronaire gauche (42 %±4). L'a. atriale antéro-médiale droite, issue de l'a. coronaire droite au niveau du tiers médial du quadrant antérieur droit du dôme atrial est l'artère la plus fréquemment en cause (50 %±5) dans la vascularisation du noeud sinuatrial. Parmi les branches de l'a. coronaire gauche, l'a. atriale antéro-médiale gauche, née au niveau du tiers médial du quadrant antérieur gauche du dôme atrial, était la branche la plus fréquemment en cause (25 %±4,3) dans la vascularisation du noeud sinu-atrial. La naissance de l'a. du noeud sinu-atrial à partir de la partie proximale ou du tronc de l'a. coronaire gauche était moins fréquente (12 %±3,2) que son origine à partir du rameau circonflexe (30 %±4,5). Les variations d'origine de l'a. du noeud sinu-atrial n'apparaissaient pas influencées par le sexe ou la race.

     

EFFICACY OF SUCRALFATE IN PREVENTING GASTROINTESTINAL SIDE EFFECTS OF NSAIDs

To find out the efficacy of sucralfate in preventing gastrointestinal side effects of non-steroidal anti-inflammatory drugs (NSAIDs) a prospective, randomised single blind study was conducted from 1989 to 1992. Patients with osteoarthritis, rheumatoid arthritis and other long standing painful conditions, who were expected to receive NSAIDs for over three months, were recruited into the study. All medicines were discontinued for a period of 10–15 days prior to initial endoscopic assessment. NSAID therapy was started and the patients were randomised to receive either placebo (group A) or sucralfate (group B) in addition. Patient were reassessed clinically every week and an endoscopic examination was repeated after 6–8 weeks of follow-up. A total of 176 patients were studied in group A (n=91) and group B (n=85). At the end of 8 weeks gastrointestinal symptoms were present in 30.6% and 26.4% patients of group A and B respectively. Endoscopic assessment showed superficial lesions in 36.5% and 18.7% while endoscopic ulcer in 2.4% and 1.1% patients of groups A and B respectively. Thus in patients receiving chronic NSAID therapy, simultaneous administration of sucralfate reduces the incidence of superficial gastric lesions but has no significant effect on symptoms or ulcer formation.KEY WORDS: Gastropathy, Sucralfate, Nonsteroidal anti-inflammatory drugs     

Reduced platelet glutamate uptake in Parkinson's disease

Summary. Defects in mitochondrial enzymes have been found not only in substantia nigra, but also in platelets from Parkinson's Disease (PD) patients, suggesting a systemic impairment of energy metabolism. Since platelets present an energy-dependent glutamate uptake similar to that described in central nervous system, glutamate uptake was determined in platelets from 34 PD patients and 21 age-related normal controls, as Na⁺-dependent [³H]glutamate influx; glutamate level was also analyzed by reverse-phase HPLC. A 50% reduction of glutamate uptake (p < 0.001) was observed in idiopathic PD patients, respect to controls and secondary parkinsonian syndromes. The decrease correlated with the severity of PD, measured by the UPDRS (r = −0.54; P < 0.05). Glutamate level was increased in platelets of PD patients, but was not correlated to the uptake decrease. Both phoenomena may be explained by the modifications of mitochondrial enzymes described in platelets, which could be used as a peripheral model of glutamatergic function in PD. Received October 7, 1998; accepted January 7, 1999