The protective mechanism of Nigella sativa against diethylnitrosamine-induced hepatocellular carcinoma through its antioxidant effect and EGFR/ERK1/2 signaling.

A wide variety of natural products have powerful chemopreventive effects due to their antioxidant, antimutagenic, and anti-inflammatory activities that enable them to arrest cell proliferation in several cancer models. In the present study, we shed light on the protective mechanism of Nigella sativa extract against diethylnitrosamine (DENA)-induced preneoplastic stage of hepatocellular carcinoma (HCC) in rats. We studied the extract effect on EGFR/ERK1/2 signaling pathway as one of the major signaling pathways controlling cell proliferation during hepatocarcinogenesis as well as the investigation of its antioxidant activity. The study also compared the effects of NSEE to those of (thymoquinone) TQ and silymarin as hepatoprotective substances. Rats received daily doses of NSEE (150, 250, 350 mg/kg BW), a dose per three alternative days/week of TQ (20 mg/kg BW) and a daily dose of silymarin (100 mg/kg BW). The doses were administered orally by gavage for 12 days before DENA and CCl4 administration, and then the supply of NSEE, TQ or silymarin was continued until the end of the experiment (16 weeks). DENA administration activated EGFR/ERK1/2 signaling and caused a significant increase in P-EGFR and P-ERK1/2 as well as a significant up-regulation of expression of target genes such as PCNA, c-fos and Bcl2, which indicated the increase in cell proliferation. Furthermore, a significant elevation in alpha-fetoprotein (AFP) and hepatic enzymes was observed in DENA-treated rats in addition to a decrease in the antioxidant status. The protection with NSEE, TQ, or silymarin has the potential to inhibit the EGFR/ERK1/2 activation and improve the antioxidant status. Moreover, the action of NSEE against the hepatocarcinogenesis was supported by high antioxidant activity and the histopathological observations of the liver. These data suggest that NSEE has a chemopreventive role in DENA-induced HCC through the inhibition of the EGFR/ERK1/2 signaling pathway and their target genes in addition to its role as an antioxidant.

Prediction of organ-specific complications following abdominal aortic aneurysm repair using cardiopulmonary exercise testing.

This study aimed at assessing whether measures of aerobic fitness can predict postoperative cardiac and pulmonary complications, 30-day mortality and length of hospital stay following elective abdominal aortic aneurysm repair. We prospectively collected cardiopulmonary exercise testing data over two years for 130 patients. Upon multivariate analysis, a decreased anaerobic threshold (OR (95% CI) 0.55 (0.37-0.84); p = 0.005) and open repair (OR (95% CI) 6.99 (1.56-31.48); p = 0.011) were associated with cardiac complications. Similarly, an increased ventilatory equivalent for carbon dioxide (OR (95% CI) 1.18 (1.05-1.33); p = 0.005) and open repair (OR (95% CI) 14.29 (3.24-62.90); p < 0.001) were associated with pulmonary complications. Patients who had an endovascular repair had shorter hospital and critical care lengths of stay (p < 0.001). Measures of fitness were not associated with 30-day mortality or length of hospital stay. Cardiopulmonary exercise testing variables, therefore, seem to predict different postoperative complications following abdominal aortic aneurysm repair, which adds value to their routine use in risk stratification and optimisation of peri-operative care.

Hypertension and treatment outcomes in Palestine refugees in United Nations Relief and Works Agency primary health care clinics in Jordan.

OBJECTIVE: In six United Nations Relief and Works Agency (UNRWA) primary health care clinics in Jordan serving Palestine refugees diagnosed with hypertension, to determine the number, characteristics, programme outcomes and measures of disease control for those registered up to 30 June, 2013, and in those who attended clinic in the second quarter of 2013, the prevalence of disease-related complications between those with hypertension only and hypertension combined with diabetes mellitus. METHOD: Retrospective cohort study with programme and outcome data collected and analysed using E-Health. RESULTS: There were 18 881 patients registered with hypertension with females (64%) and persons aged ≥ 40 years (87%) predominating. At baseline, cigarette smoking was recorded in 17%, physical inactivity in 48% and obesity in 71% of patients. 77% of all registered patients attended clinic in the second quarter of 2013; of these, 50% had hypertension and diabetes and 50% had hypertension alone; 9% did not attend the clinics and 10% were lost to follow-up. Amongst those attending clinic, 92% had their blood pressure measured, of whom 83% had blood pressure <140/90 mm Hg. There were significantly more patients with hypertension and diabetes (N = 966, 13%) who had disease-related complications than patients who had hypertension alone (N = 472, 6%) [OR 2.2, 95% CI 2.0-2.5], and these differences were found for both males [18% vs. 10%, OR 1.9, 95% CI 1.6-2.2] and females [11% vs. 5%, OR 2.4, 95% CI 2.1-2.9]. CONCLUSION: Large numbers of Palestine refugees are being registered and treated for hypertension in UNRWA primary health care clinics in Jordan. Cohort analysis and E-Health can be used to regularly assess caseload, programme outcomes, clinic performance, blood pressure control and cumulative prevalence of disease-related complications. Current challenges include the need to increase clinic attendance and attain better control of blood pressure.

Randomized clinical trial of angiotensin-converting enzyme inhibitor, ramipril, in patients with intermittent claudication.

BACKGROUND: The aim was to investigate the effect of ramipril on clinical parameters in patients with peripheral arterial disease. METHODS: Patients with intermittent claudication were randomized to receive ramipril or placebo for 24 weeks in a double-blind study. Outcome measures were walking distance, arterial stiffness measurement and quality of life (QoL). RESULTS: A total of 33 patients were included (25 men; mean(s.d.) age 64.6(7.8) years); 14 received ramipril and 19 placebo. After 24 weeks, ramipril improved maximum treadmill walking distance by an adjusted mean (95 per cent confidence interval, c.i.) of 131 (62 to 199) m (P = 0·001), improved treadmill intermittent claudication distance by 122 (56 to 188) m (P = 0.001) and improved patient-reported walking distance by 159 (66 to 313) m (P = 0.043) compared with placebo. Ramipril reduced carotid femoral pulse wave velocity by -1.47 (95 per cent c.i. -2.40 to -0.57) m/s compared with placebo (P = 0.002). Resting ankle : brachial pressure index (ABPI) improved slightly in both ramipril and placebo groups (0.02 (95 per cent c.i. -0.08 to 0.11) versus 0.03 (-0.05 to 0.10); P = 0.830). Ramipril had a slight, non-significant effect on QoL physical domains compared with placebo. CONCLUSION: Ramipril improved walking distance in patients with claudication; however, this improvement was not related to improved ABPI but might have been due to ramipril reducing arterial stiffness. REGISTRATION NUMBER: NCT01037530 (http://www.clinicaltrials.gov).

Diabetes mellitus and treatment outcomes in Palestine refugees in UNRWA primary health care clinics in Jordan.

SETTING: Six primary health care clinics in Jordan, serving Palestine refugees diagnosed with diabetes mellitus (DM). OBJECTIVES: To report on the number and characteristics of new DM patients registered in the second quarter of 2013 and of all DM patients ever registered by 30 June 2013, with treatment outcomes and cumulative burden of late-stage complications. DESIGN: A descriptive cohort study using routine data collected through e-Health. RESULTS: Of the 288 new patients in Q2 2013 and 12 548 patients ever registered with DM by 30 June 2013, smoking, physical inactivity and obesity were recorded in 19%, 50% and 47%, respectively. In Q2 2013, 9740 (78%) patients attended a clinic, with >99% having undergone disease control measures: of these, 72% had postprandial blood glucose ⩽ 180 mg/dl, 71% had blood cholesterol < 200 mg/dl, 82% had blood pressure < 140/90 and 40% had body mass index < 30 kg/m(2). Late-stage complications were present in 1130 (11.6%) patients who attended a clinic, with cardiovascular disease and stroke being the most common. Several differences in outcomes were found between males and females. CONCLUSION: There is a high burden of disease due to DM at primary health care clinics in Jordan. Cohort analysis using e-Health is a vital way to assess management and follow-up.

Endovenous laser ablation in the treatment of small saphenous varicose veins: does site of access influence early outcomes?

OBJECTIVE: The study was performed to evaluate the clinical and technical efficacy of endovenous laser ablation (EVLA) of small saphenous varicosities, particularly in relation to the site of endovenous access. METHODS: Totally 59 patients with unilateral saphenopopliteal junction incompetence and small saphenous vein reflux underwent EVLA (810 nm, 14 W diode laser) with ambulatory phlebectomies. Small saphenous vein access was gained at the lowest site of truncal reflux. Patients were divided into 2 groups: access gained above mid-calf (AMC, n = 33) and below mid-calf (BMC, n = 26) levels. Outcomes included Venous Clinical Severity Scores (VCSS), Aberdeen Varicose Vein Questionnaire (AVVQ), patient satisfaction, complications, and recurrence rates. RESULTS: Both groups demonstrated significant improvement in VCSS, AVVQ, generic quality of life Short Form 36, and EuroQol scores (P < .05) up to 1 year. No differences were seen between AMC and BMC groups for complications (phlebitis: 2 [6%] and 1 [3.8%], P > .05; paresthesia: 2 [6%] and 5 [19%], P = .223) and recurrence (3 [9%] and 1 [3.8%], P = .623), respectively. CONCLUSIONS: The site of access in our study does not appear to influence complications specifically neural injury or recurrence rates.

Intraluminal thrombus has a selective influence on matrix metalloproteinases and their inhibitors (tissue inhibitors of matrix metalloproteinases) in the wall of abdominal aortic aneurysms.

BACKGROUND: The influence of intraluminal thrombus (ILT) on the proteolytic environment within the wall of an abdominal aortic aneurysm (AAA) is unknown. This is the first study to examine the correlation between ILT thickness and the levels of matrix metalloproteinases (MMPs) and their natural inhibitors (tissue inhibitors of matrix metalloproteinases [TIMPs]) within the adjacent AAA wall. METHODS: Thirty-five patients undergoing elective repair of AAAs were studied. A single full-thickness infrarenal aortic sample was obtained uniformly from the arteriotomy site from each patient. All samples were snap frozen and analyzed for total and active MMP 2, 8, and 9 and TIMP 1 and 2. Thrombus thickness at the specimen site was measured on the preoperative contrast computed tomographic angiograms. RESULTS: There was a statistically significant correlation between ILT thickness, concentration of TIMP 1, and active concentration of MMP 9. MMP 2 (active and total) and TIMP 2 demonstrated a positive correlation with ILT thickness, although not statistically significant. CONCLUSION: In this novel study, we found a significant positive correlation of ILT thickness with active MMP 9 and TIMP 1 concentration in the adjacent AAA wall, and this may have implications for AAA expansion and eventual rupture.

Small bowel perforation due to blunt trauma to an inguinal hernia: a case report and literature review.

We report the case of a 41-year-old man with a known right inguinal hernia presenting with groin pain following a fall while dog walking. Operative findings showed a small bowel perforation affecting the loop of bowel in the hernial sac. Bowel perforations caused by blunt abdominal injury in patients with an inguinal hernia is a rare and not well recognised problem, and are confined to a handful of case reports in the surgical literature.

The attitudes of team members towards family presence during hospital-based CPR: a study based in the Muslim setting of four Iranian teaching hospitals.

BACKGROUND: Contrary to international guidelines recommending family presence during cardiopulmonary resuscitation (CPR), allowing family members to be present remains a matter of debate in many countries. The purpose of this study was to determine the opinions of healthcare providers from a Muslim setting concerning family-witnessed resuscitation (FWR). METHODS: The sample population consisted of CPR responders in four teaching hospitals in Tehran. These centres have no policy regarding the presence of family members during resuscitation. We developed and circulated a questionnaire gathering opinions, and collated their comments. RESULTS: From 200 respondents, 77% opposed FWR. We found that gender, age, experience, previous exposure to FWR or specialty (except for emergency physicians) did not predict opinion towards family presence during CPR. The most common reasons given for opposition to family presence were fear of psychological trauma to family members, possible interference with patient care/decision-making, and a perceived increase in staff stress. CONCLUSION: In a largely Muslim community, and contrary to general guidelines, our survey suggested that the majority of CPR responders do not favour the presence of relatives during cardiopulmonary resuscitation. Any counter to this opinion would need to be based on educating team members about the possible benefits of relatives being present during resuscitation. Public education surrounding CPR would also be a fundamental element for implementing any formal programme encouraging family-witnessed CPR in hospitals such as ours.

Evaluation of a new enzyme immunoassay for the detection of Helicobacter pylori in stool specimens.

H. pylori infects the gastric mucosa and causes many digestive disorders such as peptic ulcer, chronic gastritis and gastric cancer. H. pylori infection relates neither to functional health status, nor to intensity of dyspepsia. There is evidence that in most patients with H. pylori positive functional dyspepsia do not improve with eradication of the organism.This study evaluated the diagnostic accuracy of HpSA by determining the sensitivity and specificity of the stool antigen test in predicting successful eradication during and after anti microbial therapy. The work was conducted on patients who underwent upper gastrointestinal endoscopy at Al-Azhar University hospitals. Fifty patients (34 male & 16 female) with dyspepsia were selected, the exclusion criteria included use of antibiotics and proton pump inhibitors up to one month before the study. All cases were submitted to, full history, general and local examination and upper gastrointestinal endoscopy. Biopsies were taken from the antrum and body of the stomach for rapid urease test and histopathology. Stool samples were taken to detect H. pylori stool antigen. Positive patients received eradication treatment for one month and H. pylori status was re-determined by rapid urease test, histological examination and HpSA test one month later. H. pylori was detected by rapid urease test in 29 (58%) dyspeptic patient by histology in 26(52%) dyspeptic patient, while H. pylori was detected by HpSA immunoassay in 16 (32%) dyspeptic patient. The sensitivity and specificity of HpSA were 57.7% and 95.8% respectively. After successful eradication of H. pylori, reassessment by rapid urease test and histology revealed curative rate of 86.2% and 84.6% respectively, while HpSA immunoassay revealed curative rate 75%. Based on these results, the HpSA immunoassay gave sensitivity (75%) and specificity (100%). The H. pylori stool test represents an accurate and novel non-invasive concept for diagnosis of infection and can be used for daily routine in clinical practice. HpSA is a promising non-invasive test for diagnosis of H. pylori infection but may be hampered by low patient acceptability. So, HpSA is a valuable test in the pre-and post eradication assessment of infection. HpSA can be profitably employed in the primary diagnosis of H. pylori infection. This non invasive test could be very useful in investigating dyspeptic young patients. Also, it could be used profitably in epidemiological studies to determine the prevalence of H. pylori infection in the asymptomatic subjects in different communities.

Histological and histochemical studies of the accessory genital glands of buffalo-bull (Bubalis bubalis).

The vesicular, Prostate and bulbourethral glands of 38 buffalo-bulls were studied histologically and histochemically. These gland were tubulo-alveolar in type. The secretory units of the VG were lined by columnar and basal cells while those of PG and BG were lined by columnar or cuboidal cells. The glands were devoid of any glycogen or lipid. Although the PG and BG were mucoid in nature, the VG was free from neutral and acidic mucopolysaccharides. Some hydrolytic enzymes (ALKPase, ACPase, ATPase and Che) and one oxidative enzyme (SDH) were demonstrated in these glands. The results were discussed in the view of the available literature.

Use of Salt-Tolerant Lactic Acid Bacteria for Manufacture of White Pickled Cheese (Domiati) Ripened Without Salted Whey in Sealed Polyethylene Pouches.

White pickled cheeses of the Domiati type were made from a 1:1 mixture of raw cows' and buffaloes' milk (5.5% fat) with and without heating momentarily to 72°e. To cheese milk were added: (a) 6.5% salt + 2% Lactobacillus casei subsp. pseudoplantarum 333C starter, (b) 9% salt + 2% Lactobacillus casei starter, (c) 9% salt + 2% Pediococcus sp. 452 starter, (d) 9% salt + 2% Leuconostoc paramesenteroides II47 starter; control cheeses were made from raw milk with either 6.5 or 9% salt. Finished cheeses were sealed in polyethylene pouches without salted whey and ripened at ambient temperature (10-25°C) for up to 5 months. Pouch-cheeses ripened without salted whey were generally attractive, uniform creamy in color, had a firm body, waxy buttery smooth texture and a pleasant flavor. Milk with 6.5% salt appeared to be preferable to milk with 9% salt for making the cheese. The highest organoleptic scores were achieved by cheese made from milk heated momentarily to 72°C and which received 6.5% salt and 2% L. casei starter. Inoculation of both raw and heated milk containing 9% salt with either L. casei subsp. pseudoplantarum 333C, Pediococcus sp. 452 or L. paramesenteroides II47 improved cheese flavor. Limburger cheese flavor was occasionally and yeasty flavor most frequently encountered. All cheeses had high DM, fat, total and soluble N, and amino acid N, with only little loss of their nutritive constituents when compared with reported values for cheese ripened in the normal way. Increasing the salt percentage in cheese milk reduced the total protein recovered in cheese. None of the cheese components examined seemed to be associated with high flavor scores. No correlation could be established between the number and types of lactic acid bacteria found and flavor intensity.

Acetoin and Diacetyl Production by Homo- and Heterofermentative Lactic Acid Bacteria.

Eleven strains of homofermentative and heterofermentative lactic acid bacteria were screened for acetoin (A) and diacetyl (D) production from pyruvate and citrate in a peptone-yeast extract-glucose broth. The homofermenters, except Streptococcus faecalis subsp. liquefaciens , produced much more AD from pyruvate than from citrate; the opposite was true for the heterofermenters. Acetoin and diacetyl were produced from pyruvate as soon as growth was initiated. The production was exponential up to 24 h. Destruction of the accumulated AD coincided with entry into the stationary phase. Production of AD from citrate did not begin until 6 h of the logarithmic phase of growth. Formation of gas from citrate by Lactobacillus plantarum did not implicate greater ability to form AD from citrate than from pyruvate. Fifty µmoles ml-1 citrate caused about 50% inhibition of growth of Streptococcus lactis subsp. diacetylactis . All strains examined for ability to use pyruvate as a sole source of carbon were able to do so. Acetate (50 µmoles ml-1 generally stimulated AD formation from pyruvate. With the exception of a Pediococcus sp. and S. faecalis subsp. liquefaciens , acetaldehyde (100 µg ml-1) enhanced AD production but not growth. Concentrations higher than 100 µg ml-1 had different effects.

Characteristics of Salt-Tolerant Lactic Acid Bacteria, in Particular Lactobacilli, Leuconostocs and Pediococci, Isolated from Salted Raw Milk.

One hundred and fourty five lactobacilli, leuconostocs and pediococci were isolated from salted raw milks incubated at 30°C for 4 to 21 d. Of 126 lactobacilli isolated, mostly from 9 to 12% salted milk, 115 were identified as homofermentative, nonthermophilic lactobacilli-73 were classified as Lactobacillus plantarum , 31 Lactobacillus casei , 8 strains were motile and 3 Lactobacillus xylosus . The remaining 11 isolates were heterofermentative lactobacilli-8 were Lactobacillus cellobiosus and 3 Lactobacillus brevis - buchneri . Strains of L. plantarum fermented many oligosaccharides, produced DL lactate and gas from L(+) but not from D(-) tartrate and their cell wall peptidoglycan was of the mesodiaminopimelic acid type. Eight strains of L. casei proved to be subsp. pseudoplantarum on the basis of inactive lactic acid production; 8 were subsp. rhamnosus and 2 subsp. alactosus , according to their pattern of sugar fermentation. L. xylosus simulated L. casei morphologically but differed from it in fermentation of xylose. The motile strains fermented arabinose and mostly sucrose but not lactose and produced 73.2 to 94 µmoles ml-1 inactive lactate from 1 % glucose. None of 10 Leuconostoc isolates produced dextran from sucrose but they fermented trehalose and were identified with Leuconostoc paramesenteroides . Three strains belonged to Pediococcus and produced 62 µmoles ml-1 of inactive lactate, whereas other six strains were atypical pediococci. Nineteen strains representing L. plantarum , L. casei , motile strains and Pediococcus gave, on examination for isomers of lactic acid, 32.8 to 171 µmoles ml-1 inactive lactate; the L(+) enanthiomorph generally predominated.

Acetoin and Diacetyl Production by Lactobacillus plantarum Able to Use Citrate.

Whole-cell suspensions of Lactobacillus plantarum grown on lactose in the presence of citrate did not produce acetoin and diacetyl (AD) (D) from citrate in succinate buffer, pH 4.4 unless both a source of energy and nitrogen was present, but did from pyruvate. The total AD and the amount of D, produced by citrate-grown cells, from citrate were about two times the amounts formed from pyruvate, calculated on a molar basis. It appears, that AD are formed not only from pyruvate resulting from cleavage of citrate but also from acetyl-coenzyme A arising during a probable breakdown of citrate in a reversible reaction of citrate synthetase. Neither acetate nor acetaldehyde had any effect on the total AD or the amount of D produced from pyruvate by pyruvate-grown cells. The rates of AD production from pyruvate by whole-cell suspensions of pyruvate-grown L. plantarum and Streptococcus subsp. diacetylactis represented only 69.7 and 6.6%, respectively, of that produced by Lactobacillus casei . These were 0.075 µmoles/mg dry wt-1 ml-1 min-1 for L. casei , 0.053 for L. plantarum and 0.005 for S. lactis subsp. diacetylactis .

Acetoin and Diacetyl Production by Lactobacillus casei subsp. pseudoplantarum.

The ability of Lactobacillus casei subsp. pseudoplantarum to produce acetoin and diacetyl (AD) was evaluated in succinate buffer (initial pH 4.4) containing sodium pyruvate, at 30°C. Cells grown in MRS broth containing pyruvate produced AD more rapidly than did an equal number of cells either grown in broth without pyruvate or even stored, after harvesting during logarithmic growth, in MRS broth in the presence of pyruvate for 120 minutes. One or more of the enzymes catalyzing formation of AD appears to be formed originally during growth in the presence of pyruvate. The rate of AD production by pyruvate-grown cells was exponential, being 0.08 µmoles mg dry wt-1 ml-1 min-1 during the first 30 min of the reaction. Storage of pyruvate grown cells at 7°C for 6 h in 0.3 mmol/L KH2PO4 buffer, pH 7.0 resulted in 77% loss of activity. Inclusion of 0.5 ml of MRS broth in the assay mixture led to a considerable increase in AD production by both cells grown in the absence and presence of pyruvate. Lactose slightly stimulated AD production in cells grown on lactose, whereas glucose had practically no effect on glucose-grown cells. Acetate and acetaldehyde reduced AD production. The effect varied with the compound used and strain studied. Of 7 concentrations of cetylpyridinium chloride tested for their effect on AD production, the least and most inhibitory concentration were 1 and 10 µg ml-1 of assay mixture.

Acetoin and Diacetyl Formation by Streptococcus lactis subsp. diacetylactis DRC3.

Cells of Streptococcus lactis subsp. diacetylactis DRC3 which had been grown on lactose in the presence of citrate were unable to form acetoin and diacetyl (AD) from citrate when suspended in succinate buffer, pH 4.4. Inclusion of both a source of energy and nitrogen in the buffer was necessary for AD formation. Concentrations of AD and D at pH 4.4 were about five and three times the concentrations at pH 6.4. The amounts of AD and D from citrate were about eight and two times those from pyruvate, calculated on a molar basis. It appears that D, at least, is formed not only from pyruvate arising during citrate cleavage, but also from acetyl-CoA resulting from a probable citrate breakdown in a reversible reaction of a citrate synthetase. The rate of AD formation, under optimum conditions, was 0.047 µmoles mg (dry wt-1) cells ml-1 min-1. Pyruvate-grown cells produced little AD from pyruvate. AD production was inhibited partly by acetate and completely by acetaldehyde. Cetylpyridinium chloride at a concentration higher than µg ml-1 suppressed AD production from citrate because of the absence of interfering compounds normally present in milk.