Subchronic exposure to arsenic through drinking water alters expression of cancer-related genes in rat liver

Although arsenic exposure causes liver disease and/or hepatoma, little is known about molecular mechanisms of arsenic-induced liver toxicity or carcinogenesis. We investigated the effects of arsenic on expression of cancer-related genes in a rat liver following subchronic exposure to sodium arsenate (1, 10, 100 ppm in drinking water), by using real-time quantitative RT-PCR and immunohistochemical analyses. Arsenic accumulated in the rat liver dose-dependently and caused hepatic histopathological changes, such as disruption of hepatic cords, sinusoidal dilation, and fatty infiltration. A 1-month exposure to arsenic significantly increased hepatic mRNA levels of cyclin D1 (10 ppm), ILK (1 ppm), and p27(Kip1) (10 ppm), whereas it reduced mRNA levels of PTEN (1 ppm) and beta-catenin (100 ppm). In contrast, a 4-month arsenic exposure showed increased mRNA expression of cyclin D1 (100 ppm), ILK (1 ppm), and p27(Kip1) (1 and 10 ppm), and decreased expression of both PTEN and beta-catenin at all 3 doses. An immunohistochemical study revealed that each protein expression accords closely with each gene expression of mRNA level. In conclusion, subchronic exposure to inorganic arsenate caused pathological changes and altered expression of cyclin D1, p27(Kip1), ILK, PTEN, and beta-catenin in the liver. This implies that arsenic liver toxicity involves disturbances of some cancer-related molecules.     

Exotoxin activity associated with the Legionnaires disease bacterium.

Hemolysis occurred around growth of the Legionnaires disease bacterium on supplemented Mueller-Hinton agar containing sterile defibrinated blood from each of five mammalian species. Hemolysis was most pronounced with guinea pig or rabbit blood, was less intense with horse or sheep blood, and was slight with blood from a human donor. Sterile filtrates of allantoic fluid from embryonated hen's eggs that had been infected with this organism displayed hemolytic activity in a radial hemolysis assay with guinea pig cells in agar. Growth of the Legionnaires disease bacterium on F-G agar with 5% hen's egg yolk was surrounded by a zone of clearing and more circumscribed zones of iridescence and increased opacity on and in the medium. Attempts to detect activity analogous to that of Escherichia coli heat-labile or heat-stable enterotoxin in allantoic fluid from infected eggs or in cultures of the Legionnaires disease bacterium were not successful.     

Sperm binding to hyaluronan is an excellent predictor of Nili-Ravi buffalo bull fertility

This study reports the first evaluation of sperm hyaluronan binding assay (HBA) for predicting the fertility of Nili-Ravi buffalo bulls in relation to standard parameters of sperm quality. Cryopreserved semen doses of low (n = 6), medium (n = 3) and high fertility (n = 8) bulls based on their respective return rates were used. Significantly, more spermatozoa bound to hyaluronan from the most fertile bulls (57.15% ± 1.44) compared with medium (42.46% ± 1.08) and low fertility bulls (29.70% ± 0.78). A strongly positive correlation (r = .824, p < .01) was found between HBA and fertility that predicts a 67.9% variability (r² = .679, p < .01) in fertility. HBA was also strongly positively correlated with sperm viability (r = .679, p < .01) followed by their live/dead ratio (r = .637, p < .01), uncapacitated spermatozoa (r = .631, p < .01), normal apical ridge (r = .459, p < .01), motility (r = .434, p < .01), mature spermatozoa with low residual histones (r = .364, p < .01), high plasma membrane integrity (r = .316, p < .01) and nonfragmented DNA levels (r = .236, p < .05). It was negatively correlated with spermatozoa having reacted acrosome (r = −.654, p < .01). A fertility model built using a combination of sperm HBA and either sperm livability or viability predicts, respectively, 86.1% (r² = .861, p < .01) and 85.9% (r² = .859, p < .01) variability in buffalo bull fertility. In conclusion, sperm HBA may prove to be a single robust predictor of Nili-Ravi buffalo bull fertility.     

Effectiveness of the caverno-dorsal vein shunt (Barry shunt) on prolonged ischaemic priapism and its effect on the post-operative long-term erectile function

Ischaemic priapism is the most common form of priapism and requires urgent treatment. In this study, we evaluated the effectiveness of the caverno-dorsal vein shunt on resolution of ischaemic priapism and on the post-operative long-term erectile function in patients presenting with priapism. The study included 10 patients admitted to our hospital for priapism between 2010 and 2018. The median age of the patients was 31 (24–66) years. The median priapism time was 13.5 (7–38) hours. The blood gas measurements were taken from the corpus cavernosum, and the drainage of the corpus cavernosum was performed as an emergency intervention. Then, the corpus cavernosum was irrigated with 0.01% adrenaline 5 times in 20-min intervals. The caverno-dorsal vein shunt procedure was performed in cases without regression of priapism. Two months after, the operation shunt was closed. Detumescence occurred in all patients. Eight of 10 patients maintained their erectile function. In 2 patients, severe erectile dysfunction occurred at post-operative 2 months following a priapism attack and penile prosthesis implantation was performed in these 2 patients. Our study showed that caverno-dorsal vein shunt procedure is effective in providing detumescence and maintaining potency in cases with ischaemic priapism. In our opinion, caverno-dorsal vein shunt can be considered as the first treatment of choice for refractory low-flow priapism.     

Breast feeding may protect children against Campylobacter jejuni associated diarrhoea

To investigate the bacterial etiology of infant diarrhea in Karachi, Pakistan, 180 rectal swab samples collected from diarrhea patients under 5 years of age and 30 samples from age- and sex-matched healthy children were analyzed. Enteropathogenic organisms were isolated from 70 case samples (38.9%). The two most common etiologic agents were Campylobacter jejuni (19.4%) and Aeromonas hydrophilia (6.1%). Salmonella, Shigella, and Yersina appear to have a limited incidence in this age group. None of the control specimens yielded any enteropathogen. Breast-fed infants had a significantly lower risk of enteric infection. A pathogen was isolated in 26.0% of samples from breast-fed children with diarrhea compared with 46.8% of samples from bottle-fed diarrhea patients. All C jejuni infections identified in this study involved bottle-fed children. Boiled water was used to prepare infant formula in only 31.1% of these patients. These findings are consistent with those of other studies showing a decreased rate or severity of diarrhea in breast-fed infants. Mothers should be encouraged to breast feed their infants or, if this is not possible, to use boiled water for the preparation of infant formula.     

Phase II trial of gefitinib in recurrent glioblastoma.

PURPOSE: To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. PATIENTS AND METHODS: This was an open-label, single-center phase II trial. Fifty-seven patients with first recurrence of a glioblastoma who were previously treated with surgical resection, radiation, and usually chemotherapy underwent an open biopsy or resection at evaluation for confirmation of tumor recurrence. Each patient initially received 500 mg of gefitinib orally once daily; dose escalation to 750 mg then 1,000 mg, if a patient received enzyme-inducing antiepileptic drugs or dexamethasone, was allowed within each patient. RESULTS: Although no objective tumor responses were seen among the 53 assessable patients, only 21% of patients (11 of 53 patients) had measurable disease at treatment initiation. Seventeen percent of patients (nine of 53 patients) underwent at least six 4-week cycles, and the 6-month event-free survival (EFS) was 13% (seven of 53 patients). The median EFS time was 8.1 weeks, and the median overall survival (OS) time from treatment initiation was 39.4 weeks. Adverse events were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent at higher doses. Withdrawal caused by drug-related adverse events occurred in 6% of patients (three of 53 patients). Although the presence of diarrhea positively predicted favorable OS from treatment initiation, epidermal growth factor receptor expression did not correlate with either EFS or OS. CONCLUSION: Gefitinib is well tolerated and has activity in patients with recurrent glioblastoma. Further study of this agent at higher doses is warranted.     

Emergence of domestically acquired ceftriaxone-resistant Salmonella infections associated with AmpC beta-lactamase

Context  Ceftriaxone, an expanded-spectrum cephalosporin, is an antimicrobial agent commonly used to treat severe Salmonella infections, especially in children. Ceftriaxone-resistant Salmonella infections have recently been reported in the United States, but the extent of the problem is unknown. Objectives  To summarize national surveillance data for ceftriaxone-resistant Salmonella infections in the United States and to describe mechanisms of resistance. Design and Setting  Case series and laboratory evaluation of human isolates submitted to the Centers for Disease Control and Prevention from 17 state and community health departments participating in the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria between 1996 and 1998. Patients  Patients with ceftriaxone-resistant Salmonella infections between 1996 and 1998 were interviewed and isolates with decreased ceftriaxone susceptibility were further characterized. Main Outcome Measures  Exposures and illness outcomes, mechanisms of resistance. Results  The prevalence of ceftriaxone-resistant Salmonella was 0.1% (1 of 1326) in 1996, 0.4% (5 of 1301) in 1997, and 0.5% (7 of 1466) in 1998. Ten (77%) of the 13 patients with ceftriaxone-resistant infections were aged 18 years or younger. The patients lived in 8 states (California, Colorado, Kansas, Massachusetts, Maryland, Minnesota, New York, and Oregon). Nine (82%) of 11 patients interviewed did not take antimicrobial agents and 10 (91%) did not travel outside the United States before illness onset. Twelve of the 15 Salmonella isolates with ceftriaxone minimum inhibitory concentrations of 16 µg/mL or higher were serotype Typhimurium but these isolates had different pulsed-field gel electrophoresis patterns. Thirteen of these 15 isolates collected between 1996 and 1998 were positive for a 631–base pair polymerase chain reaction product obtained by using primers specific for the ampC gene of Citrobacter freundii. Conclusions  Domestically acquired ceftriaxone-resistant Salmonella has emerged in the United States. Most ceftriaxone-resistant Salmonella isolates had similar AmpC plasmid-mediated resistance.      

Oncological and cosmetic outcomes of oncoplastic breast conserving surgery.

BACKGROUND: Breast-conserving surgery and radiotherapy is firmly established as a good and safe option for most women with early breast cancer. The important outcome measures of breast conservation are survival, local recurrence, cosmesis and patient satisfaction. Partial breast reconstructive techniques may improve cosmesis and patient satisfaction without compromising the oncological outcomes. METHODS: A search of the Medline and Pubmed databases of studies on breast conserving surgery where partial breast reconstructive techniques were employed. The keywords used were breast conserving surgery, oncoplastic breast surgery, partial breast reconstruction and reduction mammoplasty. The oncological and cosmetic outcomes of these studies were analysed. RESULTS: Studies on partial breast reconstructive techniques often lack oncological outcomes and long-term results are not available. On intermediate follow-up (up to 4.5 years) local recurrence rates vary from 0 to 1.8% per year. Cosmetic failure rates vary from 0 to 18%. To date, detailed studies are small and outcome measures vary. CONCLUSIONS: Breast surgeons should be aware of the range of surgical techniques that may enhance the aesthetic results of breast-conserving surgery as well as expand the indications for its use. There is a need for routine assessment of oncological and cosmetic outcomes and long-term results of partial breast reconstructive techniques in relation to these outcomes are awaited.