Localisation of a gene for prepubertal periodontitis to chromosome 11q14 and identification of a cathepsin C gene mutation

Prepubertal periodontitis (PPP) is a rare and rapidly progressive disease of young children that results in destruction of the periodontal support of the primary dentition. The condition may occur as part of a recognised syndrome or may occur as an isolated finding. Both autosomal dominant and recessive forms of Mendelian transmission have been reported for PPP. We report a consanguineous Jordanian family with four members affected by PPP in two nuclear sibships. The parents of the affected subjects are first cousins. We have localised a gene of major effect for PPP in this kindred (Zmax=3.55 for D11S901 at θ=0.00) to a 14 cM genetic interval on chromosome 11q14 flanked by D11S916 and D11S1367. This PPP candidate interval overlaps the region of chromosome 11q14 that contains the cathepsin C gene responsible for Papillon-Lefèvre and Haim-Munk syndromes. Sequence analysis of the cathepsin C gene from PPP affected subjects from this Jordanian family indicated that all were homozygous for a missense mutation (1040A→G) that changes a tyrosine to a cysteine. All four parents were heterozygous carriers of this Tyr347Cys cathepsin C mutation. None of the family members who were heterozygous carriers for this mutation showed any clinical findings of PPP. None of the 50 controls tested were found to have this Tyr347Cys mutation. This is the first reported gene mutation for non-syndromic periodontitis and shows that non-syndromic PPP is an allelic variant of the type IV palmoplantar ectodermal dysplasias.


Keywords: prepubertal periodontitis; periodontal disease; cathepsin C; linkage     

HbA1c over 8.5% is not predictive of increased infection rate following penile prosthesis implant surgery in diabetic patients with erectile dysfunction

Diabetes mellitus is associated with increased risk of erectile dysfunction. Penile prosthesis implantation is an efficient therapeutic option for erectile dysfunction, but not without risk, as infection remains a prominent concern. This study investigates diabetes mellitus as a risk factor for penile prosthesis implantation infection and the relationship between haemoglobinA1c levels and infection rates. All diabetic patients with erectile dysfunction who underwent penile prosthesis implantation surgery between January 2012 and November 2019 at Hamad Medical Corporation, Qatar, were included in this retrospective observational study. A total of 599 diabetic patients with erectile dysfunction had penile prosthesis implantation. Mean age was 59.69 ± 31.19. Penile prosthesis implantation infection rate was 0.83% (5/599), while the mean haemoglobinA1c level was 7.58 ± 1.45 mmol/l (range: 4.1–12.6). A comparison between diabetic patients with penile prosthesis implantation infection and those without infection revealed no significant difference in the level of haemoglobinA1c between the two groups with mean haemoglobinA1c in patients with infected implants 7.14 and 7.59 for noninfected (p = 0.491). Limitations include retrospective single-centre design and low-infection rates reducing sample number. Penile prosthesis implantation infection rate in a large series of diabetic patients was low with no significant association between haemoglobinA1c level and penile prosthesis implantation infection observed.     

Changes in uptake of vitamin B(12) and trace metals in brains of mice treated with clioquinol

Clioquinol is a hydroxyquinoline antibiotic that has been associated with severe side-effects in the CNS. The syndrome caused by clioquinol treatment, subacute myelo-optic neuropathy (SMON), is considered as one of the worst drug disasters of this century. The precise biochemical mechanism behind SMON is not fully understood. Clioquinol can form strong lipophilic chelates with divalent cations and therefore it has been speculated that the drug may disturb the retention of vitamin B(12) through chelation of Co(2+). In the present study, the tissue distribution and uptake capacity of [57Co]cyanocobalamin were estimated in mice treated with clioquinol or saline. The concentrations of some trace metals were also determined in brain tissue. Accumulation of vitamin B(12) in the brain and its concentration in blood were decreased by clioquinol treatment. The mean concentrations of several trace metals were also lowered in the brain while the concentration of cobalt in the brain was not affected, suggesting that clioquinol does not bind to the cobalt in vitamin B(12). Moreover, a significant decrease in the levels of S-adenosylmethionine (SAM) was observed in the brain after clioquinol treatment. This may be a consequence of decreased vitamin B(12) levels. From these results, it can be concluded that chronic treatment with clioquinol may alter the tissue homeostasis of vitamin B(12) in the brain.     

VASCULAR SURGICAL SOCIETY: vascular surgical society of great britain and ireland

BACKGROUND: Complex limb trauma often involves combined arterial and venous injury, and the resultant ischaemia-reperfusion injury (IRI) causes both local and remote organ injury. This study assessed the influence of the timing of restoration of venous drainage on IRI. METHODS: Male New Zealand white rabbits (n = 36) were randomized into six groups: sham operation (group 1) and unilateral hind limb arterial and venous occlusion for 1 h followed by no reflow for 2 h (group 2), arterial and venous reflow for 2 h (group 3), arterial reflow alone for 2 h (group 4), arterial reflow alone for 1 h followed by arterial and venous (delayed) reflow for a further 1 h (group 5), and pretreatment with an enteral combination antioxidant before occlusion of both artery and vein and delayed venous reflow (group 6). Plasma hydroperoxide (HPO) and glutathione peroxidase concentration, hind limb skeletal muscle and lung tissue wet : dry weight ratios and myeloperoxidase (MPO) concentration were measured. RESULTS: The plasma HPO level in the femoral vein effluent was significantly greater after delayed venous reflow (mean(s.e.m.) 2. 02(0.54) micromol/l) than in control animals (0.98(0.10) micromol/l) (P < 0.05). There was also a significantly greater tissue wet : dry weight ratio after delayed venous reflow than in controls, in skeletal muscle (mean(s.e.m.) 6.89(0.14) versus 5.34(0.54); P < 0. 05) and lung (9.20(1.14) versus 7.23(0.38); P < 0.05) tissue. Lung tissue MPO activity was significantly greater after delayed venous reflow compared with controls (3.20(0.28) versus 1.86(0.14) units/g; P < 0.005), and also in comparison to simultaneous arterial and venous reflow (2.40(0.24) units/g; P < 0.05). In the antioxidant pretreatment group there was no significant increase in plasma HPO concentration, tissue MPO level or tissue wet : dry weight ratio compared with the control group. CONCLUSION: In combined major arterial and venous injury of the limb, delayed restoration of venous drainage leads to significantly greater local skeletal muscle injury and remote neutrophil-mediated lung injury. These results support the clinical rationale for early restoration not only of arterial inflow but also venous drainage by means of intraluminal shunts.     

Bilateral synchronous breast cancer: mode of detection and comparison of histologic features between the 2 breasts

BACKGROUND: Bilateral synchronous breast cancer is uncommon (accounting for 1.0%-2.6% of all patients with breast cancer), and most physicians do not accumulate a large personal experience of patients with this disease. We reviewed our experience with patients with bilateral synchronous breast cancer, focusing on the mode of detection and histologic features in the 2 breasts. METHODS: The charts of patients who were treated at this institution for bilateral synchronous breast cancer during the 15-year period of 1984 through 1999 were reviewed. Information regarding age, mode of detection, histopathologic features, treatment, and overall survival were analyzed. RESULTS: During the study period, 51 patients (all women) were treated at our institution for bilateral synchronous breast cancer. This comprised 2.1% of all patients (n = 2382 patients) treated for breast cancer during the same period of time. The first cancer was detected by palpation in 81% and by mammography in 14%. The corresponding figures for the contralateral cancer were 24% and 54%, respectively. The histologic type of cancer was identical in the 2 breasts in 29 patients (57%) and was different between the 2 breasts in 22 patients (43%). The overall 10-year survival rate was 63%. CONCLUSIONS: Bilateral synchronous breast cancer is often detected by mammography and is frequently of the same histologic type as the index cancer. A better awareness of the risk for this disease may help detect bilateral breast cancer earlier.     

Protective effect of a cysteine prodrug and antioxidant,L-2-oxothiazolidine-4-carboxylate,against ethanol-induced gastric lesions in rats

Earlier studies have suggested an important role of glutathione (GSH) in cytoprotection against free radicals induced oxidative damage. This study reports gastroprotective effects of a cysteine precursor, L-2-oxothiazolidine-4-carboxylate (OTC), in experimental models of gastric secretion and ulceration. Acid secretion studies (volume and acidity) were undertaken in pylorus-ligated rats whereas the gastric lesions were induced by ethanol. Different groups of animals were treated with OTC (0, 100, 200 and 400 mg/kg). The levels of gastric wall mucus, nonprotein sulfhydryls (NP-SH) and myeloperoxidase (MPO) were measured in the glandular stomach of rats following ethanol-induced gastric lesions. Both medium and high doses of OTC significantly reduced the volume and acidity of gastric secretion in pylorus-ligated rats. Pretreatment with OTC significantly and dose-dependently attenuated the formation of ethanol-induced gastric lesion. OTC significantly protected the gastric mucosa against ethanol-induced depletion of gastric wall mucus, NP-SH and MPO. The gastroprotective effects of OTC may be attributed to its ability to inhibit neutrophils activity and replenish GSH demand.     

Serum vitamin D status in type 2 diabetic patients from Gaza Strip

ObjectiveTo assess serum vitamin D status and its relations to other biochemical parameters in type 2 diabetic patients from Gaza Strip.Materials and methodsThis case-control study included 58 type 2 diabetic patients as well as 58 non-diabetic controls. Patients and controls were matched for age and gender. Data were obtained from questionnaire interview, and biochemical analysis of blood samples.ResultsSerum vitamin D was significantly lower in diabetic patients compared to non-diabetic controls (25.9 ± 11.0 versus 34.6 ± 13.8 ng/dl, % difference = 28.8%, P < 0.001). The number of patients having vitamin D deficient, insufficient and sufficient were 6 (10.4%), 35 (60.3%) and 17 (29.3%) compared to controls of 3 (5.2%), 16 (27.6%) and 39 (67.2%), respectively (χ² = 14.672, P < 0.001). Serum glucose, glycated hemoglobin (HbA1c), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglycerides were significantly higher in patients than in controls whereas serum insulin, high density lipoprotein cholesterol (HDL-C) and calcium were significantly lower in patients. Serum vitamin D showed significant negative correlations with HbA1c (r = ? 0.186, P = 0.046), ALT (r = ? 192, P = 0.040) and AST (r = ? 0.188, P = 0.044) whereas significant positive correlations were found with HDL-C (r = 0.188, P = 0.044) and calcium (r = 0.239, P = 0.010).ConclusionThe significant negative and positive correlations of vitamin D with HbA1c and calcium, respectively suggests that vitamin D supplementation would be of potential therapeutic value in clinical settings for controlling of type 2 diabetes and more importantly its complications. However, a well-designed clinical trials are needed to define the contribution of vitamin D status and therapy in the global diabetes problem.