Regulation of insulin secretion and proinsulin biosynthesis by succinate

Succinate stimulates insulin secretion and proinsulin biosynthesis. We studied the effects of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-modulating pathways on glucose- and succinate-stimulated insulin secretion and proinsulin biosynthesis in the rat and the insulin-resistant Psammomys obesus. Disruption of the anaplerotic pyruvate/malate shuttle by phenylacetic acid inhibited glucose- and succinate-stimulated insulin secretion and succinate-stimulated proinsulin biosynthesis in both species. In contrast, phenylacetic acid failed to inhibit glucose-stimulated proinsulin biosynthesis in P. obesus islets. Inhibition of the NADPH-consuming enzyme neuronal nitric oxide synthase (nNOS) with l-N(G)-nitro-l-arginine methyl ester or with N(G)-monomethyl-l-arginine(G) doubled succinate-stimulated insulin secretion in rat islets, suggesting that succinate- and nNOS-derived signals interact to regulate insulin secretion. In contrast, nNOS inhibition had no effect on succinate-stimulated proinsulin biosynthesis in both species. In P. obesus islets, insulin secretion was not stimulated by succinate in the absence of glucose, whereas proinsulin biosynthesis was increased 5-fold. Conversely, under stimulating glucose levels, succinate doubled insulin secretion, indicating glucose-dependence. Pyruvate ester and inhibition of nNOS partially mimicked the permissive effect of glucose on succinate-stimulated insulin secretion, suggesting that anaplerosis-derived signals render the beta-cells responsive to succinate. We conclude that beta-cell anaplerosis via pyruvate carboxylase is important for glucose- and succinate-stimulated insulin secretion and for succinate-stimulated proinsulin biosynthesis. In P. obesus, pyruvate/malate shuttle dependent and independent pathways that regulate proinsulin biosynthesis coexist; the latter can maintain fuel stimulated biosynthetic activity when the succinate-dependent pathway is inhibited. nNOS signaling is a negative regulator of insulin secretion, but not of proinsulin biosynthesis.     

Antibiotic susceptibility, serotype distribution and vaccine coverage of nasopharyngeal and oropharyngeal Streptococcus pneumoniae in a day-care centre in St. Petersburg, Russia

The objectives were to study serotypes and antibiotic susceptibility of Streptococcus pneumoniae carried by healthy children attending a day-care centre in St. Petersburg. S. pneumoniae colonization was investigated in 125 children aged 16-70 months. Antibiotic susceptibility was determined by E-test and disk diffusion. 83 S. pneumoniae cases were isolated in 75/125 (60%) children: 36/75 (48%) in the nasopharynx, 12/75 (16%) in the oropharynx and 27/75 (36%) in both. Carriage rates were 100%, 68%, 72%, 46% and 54% in children aged 12-23, 24-35, 36-47, 48-59 and >or=60 months, respectively. 97.6% of isolates were susceptible to penicillin. 61.4%, 32.5%, 19.3%, 16.7% and 6% isolates were non-susceptible to trimethoprim/sulfamethoxazole, tetracycline, clindamycin, erythromycin and chloramphenicol, respectively. 20.5% of isolates were multidrug resistant (MDR). 45% of isolates were of serotypes included in the 7-valent pneumococcal conjugate vaccine (7V-PCV); 64.9%, 56.8%, 32.4% and 27% of 7V-PCV serotypes were resistant to trimethoprim/sulfamethoxazole, tetracycline, clindamycin and erythromycin, respectively. The respective figures for MDR isolates were 100%, 94.1%, 70.6% and 76.5%; 76.5% of all MDR isolates were covered by 7V-PCV. In conclusion: 1) resistance to trimethoprim/sulfamethoxazole and tetracycline was high; 2) resistance to macrolides was higher than in other Russian regions; 3) 7V-PCV coverage was modest, but the vaccine may potentially reduce MDR-S. pneumoniae.     

Incidence and significance of a positive troponin test in bacteremic patients without acute coronary syndrome

Background

Since the introduction of troponin for the diagnosis of myocardial infarction, several studies have shown additional conditions in which troponin is elevated, including sepsis. The objective of this study was to determine the incidence of an elevated troponin in patients with bacteremia and its significance.

Methods

This was a prospective, noninterventional study. Patients with a positive blood culture were included. Cardiac troponin I (cTnI) was determined within 4 days of blood culture. A repeat electrocardiogram was obtained in a sample of patients with elevated cTnI and in patients with a negative troponin test. Demographic, clinical, and microbiological data were obtained for all patients.

Results

A total of 159 bacteremic patients were included. Positive cTnI was detected in 69 patients (43%). Elevated cTnI was associated with a number of underlying diseases, hospitalization ward, severity of the systemic inflammatory condition, and kidney function (P <.05-.001). A repeat electrocardiogram was performed in 39 patients with a positive cTnI and in 28 patients with a negative cTnI. Two of 39 patients (5%) in the positive cTnI group had ischemic changes and 2 patients (5%) had nonspecific changes, whereas only 1 patient (4%) with a negative cTnI had nonspecific changes. Bivariate analysis revealed a statistically significant association for positive cTnI and mortality; however, on multivariate analysis this was no longer significant.

Conclusion

Forty-three percent of bacteremic patients had an elevated cTnI. Risk factors for elevated cTnI were severity of the underlying infection, renal function, and underlying cardiac disease. Increased cTnI was found to be a dependent risk factor and a surrogate marker for death.     

In-hospital use of continence aids and new-onset urinary incontinence in adults aged 70 and older

OBJECTIVES: To describe the types of continence aids that older adults hospitalized in acute medical units use and to test the association between use of continence aids and development of new urinary incontinence (UI) at discharge. DESIGN: Prospective cohort study. SETTING: A 900‐bed teaching hospital in Israel. PARTICIPANTS: Three hundred fifty‐two acute medical patients aged 70 and older who were continent before admission. MEASUREMENTS: In‐hospital use of continence aids was assessed according to participant self‐report on use of urinary catheters (UCs) or adult diapers or of self‐toileting. The development of new UI was defined as participant report of inability to control voiding at discharge. Multivariate analyses modeled the association between use of continence aids (vs self‐toileting) and the development of new UI, controlling for baseline functional and cognitive status, disease severity, age, and length of stay. RESULTS: Of the 352 participants, 58 (16.5%) used adult diapers, and 27 (7.7%) had a UC during most of the hospital stay. Sixty (17.1%) participants developed new UI at discharge. The odds of developing new UI were 4.26 (95% confidence interval (CI)=1.53–11.83) times higher for UC users and 2.62 (95% CI=1.17–5.87) times higher for adult diaper users than for the self‐toileting group, controlling for the above risk factors. CONCLUSION: The use of adult diapers and UCs during acute hospitalization is associated with the development of new UI at discharge. The management of continence in hospitalized older adults requires more diligence, and further investigation is needed to devise continence promotion methods in hospital settings.     

Functional decline and satisfaction with nursing care among older hospitalized adults

Around hospitalization, older adults often experience functional decline which can be a reflection of their need for nursing care. Given a shortage of nurses, determining the relationship between functional change and patients' satisfaction with nursing care can help to gauge the need for care. We assessed this relationship in a mixed prospective‐correlational cohort study with 393 patients, 70 years or older. The art, tangible aspects and general satisfaction with nursing care were measured through interviews conducted at discharge. Patients' functional status was assessed at admission and discharge. Decline in functioning during hospitalization was the most powerful predictor of higher satisfaction with art and tangible aspects of nursing care in multivariate regression (β = 0.17–0.19, P < 0.01). This finding suggests that patients whose functioning deteriorates during hospitalization, have a greater need for and more contact with professional nursing care, and therefore report higher satisfaction with specific aspects of nursing care.     

Success of estrogen-progesterone therapy in long-standing bleeding gastrointestinal angiodysplasia

Gastrointestinal angiodysplasia is a common cause of occult bleeding. Surgical and endoscopic treatments are often ineffective. Recently, estrogen-progesterone therapy proved to be effective in these patients. We describe herein an 84-year-old man who presented with prolonged gastrointestinal bleeding, in whom treatment with estrogen-progesterone stopped the bleeding. We suggest that hormonal therapy should be considered in cases of prolonged obscure gastrointestinal bleeding thought to be due to angiodysplasia. This therapy should be instituted intermittently for a prolonged period. The role of progesterone, especially in men, should be reconsidered.