Heme is an effector molecule for iron-dependent degradation of the bacterial iron response regulator (Irr) protein

The bacterial iron response regulator (Irr) protein mediates iron-dependent regulation of heme biosynthesis. Pulse-chase and immunoprecipitation experiments showed that Irr degraded in response to 6 microM iron with a half-life of approximately 30 min and that this regulated stability was the principal determinant of control by iron. Irr contains a heme regulatory motif (HRM) near its amino terminus. A role for heme in regulation was implicated by the retention of Irr in heme synthesis mutants in the presence of iron. Addition of heme to low iron (0.3 microM) cultures was sufficient for the disappearance of Irr in cells of the wild-type and heme mutant strains. Spectral and binding analyses of purified recombinant Irr showed that the protein bound heme with high affinity and caused a blue shift in the absorption spectrum of heme to a shorter wavelength. A Cys(29) --> Ala substitution within the HRM of Irr (IrrC29A) abrogated both high affinity binding to heme and the spectral blue shift. In vivo turnover experiments showed that, unlike wild-type Irr, IrrC29A was stable in the presence of iron. We conclude that iron-dependent degradation of Irr involves direct binding of heme to the protein at the HRM. The findings implicate a regulatory role for heme in protein degradation and provide direct evidence for a functional HRM in a prokaryote.     

Cystatin C is better than albuminuria as a predictor of pulse wave velocity in hypertensive patients

Introduction: Arterial stiffness is important in the evaluation of the cardiovascular risk in both general population and hypertensive patients. In this study, we aimed to investigate the associations of both serum cystatin C levels and albuminuria with arterial stiffness in healthy controls and hypertensive patients.

Patients and methods: Seventy-six healthy controls (male/female?=?44/32) and 76 hypertensive patients (male/female?=?43/33) were enrolled. Arterial stiffness parameters such as augmentation index (AIx) and pulse wave velocity (PWV) were non-invasively measured with the Arteriograph (Tensiomed Ltd., Budapest, Hungary).

Results: AIx (31.92?±?14.31 vs. 27.95?±?11.03, p?=?0.03) and PWV (9.84?±?1.62 vs. 8.87?±?2.04, p?p?=?0.002) and higher serum cystatin C levels [0.76 (0.67–0.95) vs. 0.68 (0.62–0.78) mg/L, p?=?0.03]. In the hypertensive group, AIx was significantly correlated with PWV (r?=?0.519, p?r?=?–0.438, p?=?0.003), mean arterial pressure (MAP) (r?=?0.288, p?=?0.015) and urinary albumin–creatinine ratio (ACR) (r?=?0.386, p?=?0.004). PWV was associated with serum cystatin C (r?=?0.442, p?=?0.003) and MAP (r?=?0.377, p?=?0.001). In the linear regression analysis (model r?=?0.577, p?=?0.006) for the prediction of PWV in hypertensive patients, MAP, urinary ACR, age and serum cystatin C levels were included as independent variables. Cystatin C was found to be the significant determinant of PWV in hypertensive patients.

Conclusion: Multivariate analysis revealed that serum cystatin C but not albuminuria was significantly associated with PWV in hypertensive patients. Serum cystatin C may be better than albuminuria as a predictor of arterial stiffness in hypertensive patients.     

Radiological approach to interstitial lung disease: a guide for the nonradiologist

Articles in the past have described the radiological appearances of different interstitial lung diseases (ILDs) in varying levels of detail. However, these articles have generally been written for radiologists with a background in basic chest computed tomography (CT) interpretation. This article summarizes a basic approach for diagnosing ILDs on high-resolution CT (HRCT) for the nonradiologist clinician and discusses the most common HRCT features of common ILDs.     

Nonsense β-thalassemia mutation at codon 37 (TGG>TGA), detected for the first time in three Turkish cases

Thalassemias are genetically heterogeneous group of disorders with reduced or absent production of globin. β-Thalassemia major can be caused by homozygosity or compound heterozygosity for β-globin gene mutation. Here we report, for the first time in Turkey, three cases who carry the nonsense β-thalassemia (β-thal) mutation at codon 37 (TGG>TGA; Trp→Stop) causing premature stop codon.     

The incidence of trocar-site hernia in minimally invasive bariatric surgery: A comparison of multi versus single-port laparoscopy

Introduction

Single-port laparoscopy (SPL) employs a 1.5- to 2.5-cm incision at the umbilicus for the placement of a single working port. We hypothesized that the longer incision created by SPL compared with multiport laparoscopy may increase the incidence of trocar-site hernias. We examined our experience with SPL in bariatric operations.

Methods

There were 734 laparoscopic sleeve gastrectomy and laparoscopic adjustable gastric banding procedures performed at our institution between 2001 and 2011. Fifty-eight patients were lost to follow-up or had a short duration of follow-up (<1 month). Of the remaining 676 cases, 163 were performed via SPL. All laparoscopic wounds created by trocar size greater than 12 mm were closed with absorbable suture.

Results

Patient demographics of the SPL group and the multiport group were similar in terms of age, gender, and comorbidities. The average body mass index (BMI) of the SPL group was lower than the multiport group (43.5 ± 5.3 vs. 45.8 ± 7.7, p < 0.01). The mean follow-up for the SPL group was 11 months versus 24 months for the multiport group. There were three trocar-site hernias out of 513 cases in the multiport compared to one hernia out of 163 cases in the SPL group (0.6 vs. 0.6 %, p = 0.967). All trocar-site hernias occurred at the 15-mm port site. The median time to hernia occurrence for the multiport group was 13 months (range, 1–18). In the SPL group, the hernia occurred at 8 months. On multivariate analysis, age, BMI, SPL, procedure type, and the postoperative weight loss were not associated with the development of trocar-site hernias.

Conclusions

SPL did not increase the rate of trocar-site hernia in this series. A low rate of trocar-site hernia can be achieved with the use of SPL in bariatric surgery.     

Influence of parity on bone mineral density and peripheral fracture risk in Moroccan postmenopausal women

The aims of the study were to determine: (1) the relationship between parity and bone mineral density (BMD); (2) the relationship between parity and osteoporotic peripheral fractures.

Material and methods

The group studied included 730 postmenopausal women. Patients were separated into four groups according to the number of fullterm pregnancies, group 1: nulliparae, group 2: one to three pregnancies, group 3: four to five pregnancies, and group 4: six and more pregnancies. Additionally, patients were separated into three groups according to their ages, as <50 years, 50–59 years and ≥60 years.

Results

The median parity was 4 [0–20]. All the patients with parity greater than six had spine and hip BMD values significantly lower than values in the other groups (p < 0.001). After adjustment for age and body mass index (BMI), decreased lumbar and total hip BMD were still associated to increased parity (analysis of covariance (ANCOVA), p = 0.04 and 0.023, respectively). The relation between parity and lumbar BMD was highly significant among women aged <50 years (age-adjusted p = 0.022), while there was no parity-spine BMD association in the other age groups. The relation between parity and hip BMD was seen only in the group 50–59 years (age-adjusted p = 0.042). A positive history for peripheral fractures was present in 170 (23%) patients. There was relationship between parity and peripheral fractures neither in the whole population nor in the sub-groups according to age.

Discussion

The present study suggests that the BMD of the spine and hip decreases with an increasing number of pregnancies, and this situation shows variations in different age groups. However, there was no correlation between parity level and peripheral fractures.