The hydrogen sulfide donor,Lawesson's reagent,prevents alendronate-induced gastric damage in rats

Our objective was to investigate the protective effect of Lawesson''s reagent, an H₂S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson''s reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson''s reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm²); increased levels of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson''s reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm²); reduced TNF-α, IL-1β, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson''s reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson''s reagent. Our results suggest that Lawesson''s reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (K_ATP) channels.     

Klinefelter's Syndrome: Hypogonadism,abnormal carbohydrate metabolism. Is it a result of biotin deficiency?

The aetiology of Klinefelter's Syndrome is not known. The causative factor(s) must explain the hypogonadism, low androgen levels, the disordered carbohydrate metabolism and the commonly associated psychiatric conditions. A biotin deficient/dependent state can account for the above. A biotin deficient Klinefelter's Syndrome patients with the above is described. The possible role of biotin in the primary, secondary and tertiary prevention of Klinefelter's Syndrome needs further research.     

Osteohistological correlates of muscular attachment in terrestrial and freshwater Testudines

Sharpey's fibers are considered the anatomical structures integrated to the muscles. Since these fibers leave marks at the microscopic level, their presence and distribution are used as evidence of muscle attachment in extinct and extant forms. In recent years, studies have been focusing on muscle–bone and tendon–bone interaction mostly on mammals. The main objective of this work is to contribute to the morphological and histological knowledge of muscle attachment in other amniotes, such as reptiles, and their variation related to different locomotor habits. In this way, a study was performed on terrestrial and aquatic turtles. The musculature related to the movement of the humerus, and pectoral girdle in Chelonoidis chilensis, Phrynops hilarii and Hydromedusa tectifera was analyzed. Dissections were performed mapping the origins and insertions of each muscle and undecalcified thin sections were performed in specific muscular attachment sites. We found some differences which were not previously reported, related to the insertion of the m. pectoralis, the m. coracobrachialis magnus and the origin of the m. tractor radii. The osteohistology revealed the presence of Sharpey's fibers in the cortex of all the bone elements analyzed. Patterns were established in relation to the orientation and density of Sharpey's fibers, which were used for the categorization of each muscle attachment site. The comparative micro‐anatomical study of these areas did not reveal any important differences between terrestrial and freshwater turtles in muscles involved with the rotation, abduction and adduction of the humerus. In this way, the preliminary results suggest an absence of correlation between the distribution and density of Sharpey's fibers between different habitat forms, at least in the bones and species analyzed.     

Extensive loss of choline acetyltransferase activity is not reflected by neuronal loss in the nucleus of meynert in Alzheimer's disease

Choline acetyltransferase activity in discrete tissue punches from the nucleus of Meynert and in tissue from the temporal cortex was reduced by at least 90% and 75%, respectively, in 5 out of 6 elderly cases of Alzheimer's disease compared with 5 normal cases. In contrast, estimates of neurone density in these same cases revealed that there was only, on average, a 33% neurone loss in the nucleus of Meynert in Alzheimer's disease. These observations suggest that a key pathological change in Alzheimer's disease may be the ‘down regulation’ of transmitter-specific enzyme production in cholinergic neurones, and that neurone loss itself may be a secondary feature of the disease.     

The effect of exposure conditions upon the release of soluble copper and tin from dental amalgams

The concentrations of soluble copper and tin which were generated by the corrosion of a number of different amalgams in both an artificial saliva and Ringer's solution are reported. Besides variations in solution composition, the effects of solution agitation and abrasive particle wear upon the release of soluble species are studied Immersion only, moderate solution agitation, vigorous solution agitation with abrasive particle wear, and accelerated corrosion by both constant currents and cyclic voltammetry are included. The results indicate that an artificial saliva but not Ringer's solution is capable of generating high levels of soluble tin. With artificial saliva, agitation increases the amalgam weight losses and increases soluble copper and tin concentrations, whereas agitation with Ringer's solution decreases sample weight losses and decreases levels of soluble copper and tin. This latter effect is believed to be due to the increased oxygen supply to the amalgam surfaces with agitation and the greater ability for producing protective passivating films of the basic hydroxide and copper chlorides in solutions of higher chloride ion concentrations e.g. Ringer's solution. Abrasive particle wear, including pumice, alumina, glass beads, and silica gel had varied effects upon the release of soluble species. Depending upon the amalgam, the solution, and the abrasive combination, either larger increases in copper or in tin occurred or reduced concentrations.     

Novel autoantibodies in Sjögren's syndrome: A comprehensive review

Sjögren's syndrome is a systemic autoimmune disease characterized by immune- mediated injury of exocrine glands, as well as a diverse array of extraglandular manifestations. B cell over-activation is a key feature of the disease, attested by the wide spectrum of autoantibodies detected in these patients. Up to date, anti- Ro/SSA and anti-La/SSB antibodies are traditional biomarkers for disease classification and diagnosis. On the other hand, the detection of novel autoantibodies in SS has increased in the last years, opening a window of opportunity to denote particular stages of the disease, to establish clinical phenotypes, and to predict long-term complications such as lymphoma. For instance, anti-SP-1, anti-CA6 and anti-PSP antibodies occur in an earlier stage than anti-Ro/La antibodies, and may identify a subset of primary Sjögren's syndrome patients with mild or incomplete disease, whereas anti-cofilin-1, anti- alpha-enolase and anti-RGI2 antibodies are potential biomarkers of MALT lymphoma. Antibody detection is also important to elucidate new aspects of SS pathophysiology, and in the future to permit a phenotype-specific patient approach. Herein we review the literature regarding new autoantibodies in SS and attempt to dissect their usefulness as diagnostic tools, pathogenic role, identification of clinical phenotypes and as predictors of an overlap syndrome.     

A method for isolation and culture of lymphocytes from endoscopic biopsies

Human small and large intestinal lamina propria lymphocytes have been successfully prepared from endoscopic biopsies by a combined enzymatic and mechanical method which gives higher yields of viable mucosal lymphocytes than previously reported, despite the small size of the biopsy samples. Viability of the cells was demonstrated by dye exclusion and they could be satisfactorily maintained in short-term culture. Phytohaemagglutinin-P (PHA-P) transformation characteristics of intestinal lymphoid cells and those of peripheral blood were studied in 20 patients with Crohn's disease and 10 control subjects. Peripheral blood lymphocytes were separated according to this technique, no decrease in viability being observed when compared to a standard Ficoll-Hypaque gradient technique. Endoscopically abnormal (EA) and endoscopically normal (EN) Crohn's tissue showed significantly different responses to PHA-P (P<0.001), EA tissue lymphocytes giving lower blastogenic responses.     

Choline acetyltransferase immunohistochemistry in brains of alzheimer's disease patients and controls

Choline acetyltransferase (ChAT)-containing neuronal structures of the basal forebrain were studied by ChAT immunohistochemistry in the brains of persons dying with Alzheimer's disease (SDAT), as well as age-matched controls dying without neurological disorder. A loss of >50% in ChAT-containing neurons was found in the substantia innominata in the SDAT group. In contrast, there was no reduction in the number of ChAT-containing neurons of the putamen as compared with controls. The data confirm the reason for the reduction of ChAT as measured biochemically in the neocortex of SDAT cases, and support the cholinergic hypothesis of memory.     

The digestive system in psychosomatic perspective

Improved understanding of the digestive organ's various levels of regulation and the neurologic and endocrinologic mechanisms underlying them should be combined with an appreciation of the variability of the individual's view of and hence response to life experiences. This balanced perspective will aid the clinician in his approach to patients with digestive disorders.     

A rationale for studying the transmissibility of Alzheimer's disease

—Despite extensive chemical, epidemiological, histopathological and pharmacological investigations of Alzheimer's disease (AD), its etiology remains elusive. This article describes studies supporting a rationale for exploring a transmissible slow viral etiology of at least some forms of AD. To date, a major limitation in these studies has been reliance upon induction of AD hispathology as the outcomes measure of successful transmission. Future studies should consider novel outcome measures for the detection of success although hispathologically inapparent, transmissible infection. In addition, the need to inoculate a diverse variety of rationally selected, potential hosts is stressed.     

The pathology of the heart in progressive muscular dystrophy: Epimyocardial fibrosis

The gross and microscopic appearance of the hearts from eight patients with Duchenne's progressive muscular dystrophy are described. Seven hearts had gross evidence of myocardial fibrosis, five of these demonstrating distinctive fibrosis of the epimyocardial portion of the free wall of the left ventricle, often with a striking band-like appearance. On the basis of mapping studies of the myocardial fibrosis, a theory regarding the progression of myocardial fibrosis in Duchenne's progressive muscular dystrophy is presented. Correlation of the pathologic anatomy, electrocardiograms, and vectorcardiograms in these patients and the family studies of others suggests that Duchenne's progressive muscular dystrophy represents a generalized cardiomyopathy that has its gravest and most distinctive effect on the epimyocardial portion of the free wall of the left ventricle.     

Dopamine and methionine-enkephalin in human brain

The contents of dopamine (determined radioenzymatically) and methionine-enkephalin (assayed by a radioimmunoassay) were measured in several areas of the human brain. The peptide was principally localized in dopamine-rich structures. In patients with Parkinson's disease, in contrast to the general dopamine deficiency, the reduction in methionine-enkephalin was restricted to the mesencephalon, putamen and lateral pallidum.     

Purine‐related metabolites and their converting enzymes are altered in frontal,parietal and temporal cortex at early stages of Alzheimer's disease pathology

Adenosine, hypoxanthine, xanthine, guanosine and inosine levels were assessed by HPLC, and the activity of related enzymes 5′‐nucleotidase (5′‐NT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) measured in frontal (FC), parietal (PC) and temporal (TC) cortices at different stages of disease progression in Alzheimer''s disease (AD) and in age‐matched controls. Significantly decreased levels of adenosine, guanosine, hypoxanthine and xanthine, and apparently less inosine, are found in FC from the early stages of AD; PC and TC show an opposing pattern, as adenosine, guanosine and inosine are significantly increased at least at determinate stages of AD whereas hypoxanthine and xanthine levels remain unaltered. 5′‐NT is reduced in membranes and cytosol in FC mainly at early stages but not in PC, and only at advanced stages in cytosol in TC. ADA activity is decreased in AD when considered as a whole but increased at early stages in TC. Finally, PNP activity is increased only in TC at early stages. Purine metabolism alterations occur at early stages of AD independently of neurofibrillary tangles and β‐amyloid plaques. Alterations are stage dependent and region dependent, the latter showing opposite patterns in FC compared with PC and TC. Adenosine is the most affected of the assessed purines.     

Lemmel's Syndrome,an Unusual Cause of Abdominal Pain and Jaundice by Impacted Intradiverticular Enterolith: Case Report

Duodenal diverticula are detected in up to 27% of patients undergoing upper gastrointestinal tract evaluation with periampullary diverticula (PAD) being the most common type. Although PAD usually do not cause symptoms, it can serve as a source of obstructive jaundice even when choledocholithiasis or tumor is not present. This duodenal diverticulum obstructive jaundice syndrome is called Lemmel''s syndrome. An 81-yr-old woman came to the emergency room with obstructive jaundice and cholangitis. Abdominal CT scan revealed stony opacity on distal CBD with CBD dilatation. ERCP was performed to remove the stone. However, the stone was not located in the CBD but rather inside the PAD. After removal of the enterolith within the PAD, all her symptoms resolved. Recognition of this condition is important since misdiagnosis could lead to mismanagement and therapeutic delay. Lemmel''s syndrome should always be included as one of the differential diagnosis of obstructive jaundice when PAD are present.

Graphical Abstract

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The population prevalence of Down's syndrome in England and Wales in 2011

There is uncertainty over the population prevalence of people with Down''s syndrome in England and Wales. This study aimed to estimate the population prevalence of Down''s syndrome in England and Wales in 2011. A meta-analysis of published survival rates of people with Down''s syndrome from 1938 to 2010 was conducted and the results were applied to the estimated numbers of babies born with Down''s syndrome since 1938 in England and Wales. An estimated 37 090 people had Down''s syndrome in England and Wales in 2011, a population prevalence of 0.66 per 1000 people; 650 under 1, 2673 aged 1–5, 7115 aged 5–18, 12819 aged 19–40, 10 626 aged 41–55 and 3207 aged 56 and older. The average life expectancy for babies with Down''s syndrome born in 2011 was 51 years and the median life expectancy was 58 years. This study provides clarity on the number of people with Down''s syndrome in England and Wales. Owing to sudden increases in the survival of babies with Down''s syndrome in the 1950s there are a large proportion of people with Down''s syndrome who are in their 40s. These people have an increased risk of developing dementia in the future and services should be aware of their potential needs.     

Pocket calculator program: Welch's v statistic

A program written for the Hewlett-Packard HP $\text{29}\text{19}\text{C}$ programmable calculator is presented which will calculate the Welch's v statistic for use in comparing means from normally distributed data with unequal sample sizes and variances.     

The effect of cimetidine on immunological parameters in Crohn's disease: A double blind trial

Thirty-six patients with Crohn's disease were entered into a double-blind trial to assess any beneficial effect that cimetidine might have on immunological and clinical status. Eighteen patients were randomized to receive cimetidine, 1 g orally for 28 days, and the other 18 patients to receive a placebo. There was no alteration in clinical status in the cimetidine-treated group. Although 64% of the patients were anergic, augmentation of skin tests to candida, mumps, tuberculin, streptokinase/streptodornase and trichophyton antigens, was not observed in the cimetidine-treated patients. The patients with Crohn's disease, as a whole had higher absolute numbers of suppressor T-lymphocytes, 0.70 × 10⁹/litre (0.21?2.36, n = 35) compared to control values, 0.5 × 10⁹/litre (0.16–1.55, n = 25) (P < 0.05). However, there was no significant difference in proportions of suppressor and helper T-lymphocytes, lymphocyte activation and humoral immunity after cimetidine treatment. The lack of any clear modulation of immunity by cimetidine, would be against trying H₂ antagonists in a long term clinical trial.     

Expression of cytokines,chemokines and other effector molecules in two prototypic autoinflammatory skin diseases,pyoderma gangrenosum and Sweet's syndrome

Pyoderma gangrenosum (PG) and Sweet''s syndrome (SS) are two inflammatory skin diseases presenting with painful ulcers and erythematous plaques, respectively; both disorders have a debilitating clinical behaviour and PG is potentially life-threatening. Recently, PG and SS have been included among the autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T cells. However, an autoinflammatory pattern clearly supporting this inclusion has never been demonstrated. We studied 16 patients with PG, six with SS and six controls, evaluating, using a sandwich-based protein antibody array method, the expression profile of inflammatory effector molecules in PG, SS and normal skin. The expressions of interleukin (IL)-1 beta and its receptor I were significantly higher in PG (P = 0·0001 for both) and SS (P = 0·004–0·040) than in controls. In PG, chemokines such as IL-8 (P = 0·0001), chemokine (C-X-C motif) ligand (CXCL) 1/2/3 (P = 0·002), CXCL 16 (P = 0·003) and regulated upon activation normal T cell expressed and secreted (RANTES) (P = 0·005) were over-expressed. In SS, IL-8 (P = 0·018), CXCL 1/2/3 (P = 0·006) and CXCL 16 (P = 0·036) but not RANTES were over-expressed, suggesting that chemokine-mediated signals are lower than in PG. Fas/Fas ligand and CD40/CD40 ligand systems were over-expressed in PG (P = 0·0001 for Fas, P = 0·009 for Fas ligand, P = 0·012 for CD40, P = 0·0001 for CD40 ligand), contributing to tissue damage and inflammation, while their role seems to be less significant in SS. Over-expression of cytokines/chemokines and molecules amplifying the inflammatory network supports the view that PG and SS are autoinflammatory diseases. The differences in expression profile of inflammatory effectors between these two disorders may explain the stronger local aggressiveness in PG than SS.     

Central amine metabolism in Alzheimer's disease: In vivo relationship to cognitive deficit

Levels of the amine metabolites homovanillic acid (HVA) and methoxyhydroxyphenylglycol (MHPG) were measured in the cerebrospinal (CSF) fluid of drug-free patients with Alzheimer's disease and compared to levels in a group of controls. No significant differences were found in CSF HVA and MHPG, although the Alzheimer's group was severely demented. Platelet monoamine oxidase (MAO) enzyme kinetics were measured and did not differ between controls and Alzheimer patients. The degree of dementia did not show any significant correlation with the levels of HVA or MHPG. It was concluded that, unlike previous reports in the literature, the dementia of Alzheimer's disease was not related to changes in central catecholamine metabolism nor was it associated with increased platelet MAO activity.     

Parkinson's disease: A disorder due to nigral glutathione deficiency?

Amino acid analysis of autopsied human brain showed reduced glutathione (GSH) content significantly lower in the substantia nigra than in other brain regions. GSH was virtually absent in the nigra of patients with Parkinson's disease. Oxidative degradation of l-DOPA and dopamine in vivo may generate reactive oxygen species (hydrogen peroxide, superoxide, hydroxyl radical, or singlet oxygen) which can damage membranes and other cellular components. Since GSH is an important natural antioxidant, a deficiency of GSH in the substantia nigra could make this region vulnerable to oxidative injury. If confirmed, the hypothesis that loss of nigrostriatal dopaminergic neurons results from a regional GSH deficiency could have important therapeutic implications for the management and prevention of Parkinson's disease.