Regulation of hepatocyte activator inhibitor-1 expression by androgen and oncogenic transformation in the prostate

Hepatocyte activator inhibitor-1 (HAI-1) is a transmembrane serine protease inhibitor that regulates the conversion of latent to active hepatocyte growth factor (HGF). Studies supporting a role for the HGF pathway in prostate carcinogenesis prompted an analysis of HAI-1 expression in the prostate. Here we analyze the regulation of HAI-1 expression by androgen, oncogenic transformation, and cancer progression. Immunohistochemical analysis revealed that HAI-1 expression was restricted to prostate epithelium, where staining occurred primarily in basal and atrophic luminal epithelial cells. Compared to normal glands, HAI-1 expression was significantly increased in localized prostate cancer and was present in most prostate cancer metastases. HAI-1 protein expression levels were sensitive to androgen in normal epithelium but not in cancer. Although androgen did not increase HAI-1 protein expression levels in LNCaP cells, it decreased HAI-1 surface expression, consistent with previous data from our group (Martin DB, Gifford DR, Wright ME, Keller A, Yi E, Goodlett DR, Aebersold R, Nelson PS: Quantitative proteomic analysis of proteins released by neoplastic prostate epithelium. Cancer Res 2004, 64:347-355). HAI-1 overexpression in cancer was predictive of prostate-specific antigen recurrence (relative risk, 1.24). These results suggest that HAI-1 regulates the HGF Met axis on prostate epithelial cells and influences HGF mediated tumor invasion and metastasis.     

BRCA2 founder mutation in Slovenian breast cancer families

Linkage analysis has identified BRCA1 and BRCA2 germline mutations as the major cause for cancer predisposition in breast and/or ovarian cancer families. In previous screening efforts on Belgian families we had a BRCA1/2 gene mutation detection rate of 25%.(1) Here we report the results of a BRCA mutation screening in seven high-risk breast/ovarian cancer families from Slovenia. We found a single but highly recurrent BRCA2 splice site mutation (IVS16-2A>G) in three breast cancer-only families. This cancer-linked mutation could not be identified in three families with ovarian cancer, suggesting that the mutation predisposes at least predominantly to breast cancer. All mutation carriers shared a common disease associated haplotype indicating a founder effect. This mutation most probably occurred in a single ancestor and seems essentially confined to the Slovene population.     

Escherichia coli biofilm formation and dispersion under hydrodynamic conditions on metal surfaces

The aim of this study was to analyze the impact of hydrodynamic forces on the multiplication of E. coli, and biofilm formation and dispersion. The experiments were provided in a flow chamber simulating a cleaning-in-place system. Biofilm biomass was measured using a crystal violet dye method. The results show that hydrodynamic forces affect not only biofilm formation and dispersion but the multiplication of E. coli in the first place. We found more biofilm biomass on the rough surface than on the smooth one. The results of the biofilm formation test show that laminar flow promotes the biofilm growth over 72 h, meanwhile turbulent flow after 48 h causes decrease in biomass. The results of the biofilm dispersion test, in contrast, show that laminar flow removed less biofilm from both materials that turbulent flow did. Therefore, taking into account these findings in cleaning-in-place technology can substantially reduce E. coli multiplication and biofilm formation.     

Uncommon combination of multiple myeloma in three patients

The authors describe uncommon combinations of multiple myeloma in three men aged 83, 63 and 55 years. In patient no. 1 both diseases--pernicious anaemia and multiple myeloma IgG-kappa were detected simultaneously. In patient no. 2 Crohn's disease preceded multiple myeloma IgA-lambda by more than 30 years. In patient no. 3 Gaucher's disease preceded multiple myeloma with paraproteinaemia IgA-lambda and IgG-kappa by more than 10 years. The diagnosis was facilitated by examination of the bone marrow, immunochemical examination of serum and urine and X-ray examination of the skeleton. In all patients the development of the myeloma had an adverse effect on the general course of the disease and despite treatment it soon proved fatal. In the discussion views on the possible causal associations between these diseases are discussed.     

Anesthetic Efficacy of Meperidine in Teeth With Symptomatic Irreversible Pulpitis

Achieving adequate pulpal anesthesia in mandibular teeth is always a challenge. Supplementary injections and using drugs in combination are some methods implemented to overcome this hurdle. In this randomized clinical trial, use of meperidine in conjunction with lidocaine in intraligamentary injection did not exhibit significant improvement in anesthesia.Key Words: Periodontal ligament, Meperidine, Irreversible pulpitis, Dental anesthesiaThe failure rate of the inferior alveolar nerve block (IANB) in some experimental studies has been reported up to 75%.^1–4 This lack of success has even increased to a maximum of 81% in some recent studies.^5–7 To overcome this shortcoming, dental clinicians have actively sought measures to improve the patients'' anesthesia during different dental procedures. Apart from the anatomical variations mentioned in the applied anatomy of injections,⁸ several authors have attempted to modify the anesthetic technique,^9–12 and others have compared different anesthetic agents¹³ or their concentrations¹⁴ to improve their efficacy.Activating the opioid receptors peripherally in inflammatory conditions has become a new trend in research to manage postoperative pain.¹⁵ Synergy between local anesthetics and opioids has become an interesting field of research recently.¹⁶ Opioids are frequently added to local anesthetics in a variety of surgical procedures, eg, intrathecal application for minor surgery.¹⁷ Meperidine or its derivatives, eg, pethidine (meperidine chloride) or norpethidine (Pethidine Intermediate B) are agonists of μ-opioid receptors, which block the pathway of pain signals to the trigeminal nucleus. They also activate peripheral opioid receptors and block sodium channels.^17–22 Despite controversy regarding the use of meperidine as an anesthetic,²² recent studies have demonstrated its benefits over prilocaine in arthroscopy with local anesthesia,¹⁶ nasal packing removal,²³ etc.However, only a few studies have investigated the dental anesthetic efficacy of such combinations.^24,25 The effect of the addition of meperidine to lidocaine in IANB for pain management in normal teeth²⁴ and also in teeth with irreversible pulpitis²⁵ has been studied. The aim of our study was to compare the efficacy of local anesthetics with and without meperidine for intraligamentary supplemental injection for teeth with irreversible pulpitis. Our null hypothesis stated that the addition of meperidine to standard lidocaine with epinephrine does not improve the efficacy of supplemental intraligamentary anesthesia in teeth with symptomatic irreversible pulpitis. The specific objectives were to randomly allocate volunteers with complete soft tissue anesthesia following an IANB, yet having positive pulp response, into 2 groups, and then compare the efficacy of lidocaine with epinephrine plus meperidine with that of lidocaine with epinephrine plus an equal volume of sterile water for supplemental periodontal ligament anesthesia.     

Menace of childhood non-accidental traumatic brain injuries: A single unit report

Background:

Childhood traumatic brain injury (TBI) has high rate of mortality and morbidity worldwide. There are dearths of reports from developing countries with large paediatric population on trauma; neurosurgery trauma of nonaccidental origin is not an exemption. This study analysed menace of non-accidental TBI in the paediatric population from our center.

Materials and Methods:

This is a single unit, retrospective study of the epidemiology of non-accidental TBI in children starting from September, 2008 to March, 2014. The management outcomes of the epidemiology of the non-accidental TBI were analysed.

Results:

Total of 109 children age range from 0 (intra-natal) to 16 years with a mean of 5.8 ± 4.6 years (median, 5 years) were enrolled into the study. 34 (31.2%) were domestic violence, 26 (23.9%) street assaults, 16 (14.7%) were due to animal assaults and mishaps, 17 (15.6%) fall from heights. Seven (6.4%) cases of collapsed buildings were also seen during the period. Four (3.7%) industrial accidents and two (1.8%) were self-inflicted injuries. There were also three (2.8%) cases of iatrogenic TBI out of which two infants (1.8%) sustained TBI from cesarean section procedure while one patient (0.9%) under general anaesthesia felt from the operation bed resulting to severe TBI.

Conclusion:

Child abuse, unprotected child labour, parental/care-givers negligence are the main cause of nonaccidental TBI. Human right activists and government agents should be incorporated in curtailing the menace.