Hyperglycemia exaggerates ischemia-reperfusion-induced cardiomyocyte injury: reversal with endothelin antagonism

OBJECTIVES: We have previously demonstrated an importance of endothelin-1 in diabetic patients undergoing bypass surgery. Recent evidence suggests that cardiomyocytes might also produce endothelin-1, which might directly impair myocyte contractility by increasing intracellular calcium levels. Because hyperglycemia is a potent stimulus of endothelin-1 production, we hypothesized that increased production, action, or both of endothelin-1 might be a mediator of direct cardiomyocyte injury in diabetes. Therefore we studied the effects of endothelin receptor blockers (BQ-123 and bosentan) on hyperglycemia-induced endothelin-1 production and cellular injury after ischemia-reperfusion. METHODS: Using a human ventricular heart cell model of simulated ischemia-reperfusion, we studied the effects of normoglycemia (5 mmol/L, 48 hours) and hyperglycemia (25 mmol/L, 48 hours) on cellular injury and endothelin-1 production. Furthermore, the effects of selective endothelin-A and mixed endothelin-A/B receptor antagonism (with BQ-123 and bosentan, respectively) were evaluated. RESULTS: Cellular injury, as assessed by means of trypan blue uptake, was higher in human ventricular heart cells subjected to hyperglycemia and simulated ischemia-reperfusion injury (P =.01); this effect was prevented with both BQ-123 and bosentan (P =.01). In addition, heart cells from the hyperglycemic group elaborated more endothelin-1 after ischemia-reperfusion (P =.02). CONCLUSIONS: Endothelin-1 production and cellular injury were greater in human ventricular heart cells subjected to hyperglycemic conditions and simulated ischemia-reperfusion. These effects are mediated by endothelin-A receptors because both BQ-123 and bosentan exerted similar degrees of protection. Endothelin receptor blockade is a novel strategy to improve the resistance of the diabetic heart to cardioplegic arrest and reperfusion.     

Ursodeoxycholic Acid Enhances Fractional Calcium Absorption in Primary Biliary Cirrhosis

Bone disease is a frequently reported complication in primary biliary cirrhosis (PBC), but its pathogenesis is poorly understood. Calcium malabsorption has been considered as an important contributing factor. Ursodeoxycholic acid (UDCA) is the treatment of choice in PBC, improving survival, but its effect on calcium absorption is unknown. In this study, we have measured fractional calcium absorption, using a single isotope method, in a group of female PBC patients (median age: 60 years, range: 46–78 years) and age-matched female controls (median age: 58 years, range: 36–74). Bone mineral density (BMD) in PBC patients was significantly lower than age-matched controls (g/cm²± SEM; lumbar spine: controls 1.139 ± 0.028, PBC patients 1.004 ± 0.026, p= 0.0028; femoral neck: controls 0.944 ± 0.034, PBC patients 0.819 ± 0.023, p = 0.0032). Twenty two PBC patients, who were not vitamin D-deficient, were off and on UDCA for ~1 month and ~8 weeks, respectively. Fractional calcium absorption in PBC patients prior to UDCA treatment (mean ± SEM, 33.8 ± 2.6%) was significantly lower than controls (52.0 ± 2.4%, p<0.001). Following UDCA therapy, fractional calcium absorption increased significantly (Off UDCA: 33.1 ± 2.6%, On UDCA: 36.6 ± 2.5%, p<0.0058). Osteocalcin levels were significantly raised in the PBC group (mean ± SEM, ng/ml, 41.4 ± 2.02) compared to controls (31.1 ± 2.64, p= 0.002). There were no differences in parathyroid hormone (PTH) or 25-hydroxyvitamin D levels between these two groups or following UDCA therapy. In conclusion, we found that PBC patients display low spinal and femoral neck BMD, reduced fractional calcium absorption, and elevated plasma osteocalcin. The calcium malabsorption is corrected partially by UDCA therapy. Long-term studies are required to determine whether this effect can be sustained, and whether a sustained increase in fractional calcium absorption can translate into a favorable change in bone strength in patients with PBC. Received: 27 November 2001 / Accepted: 11 April 2002     

Effect of highly purified capsaicin on articular cartilage and rotator cuff tendon healing: An in vivo rabbit study

Highly purified capsaicin has emerged as a promising injectable compound capable of providing sustained pain relief following a single localized treatment during orthopedic surgical procedures. To further assess its reliability for clinical use, the potential effect of highly purified capsaicin on articular cartilage metabolism as well as tendon structure and function warrants clarification. In the current study, rabbits received unilateral supraspinatus transection and repair with a single 1 ml injection of capsaicin (R + C), PEG‐only placebo (R + P), or saline (R + S) into the glenohumeral joint (GHJ). An additional group received 1 ml capsaicin onto an intact rotator cuff (I + C). At 18 weeks post‐op, cartilage proteoglycan (PG) synthesis and content as well as cell viability were similar (p > 0.05) across treatment groups. Biomechanical testing revealed no differences (p > 0.05) among tendon repair treatment groups. Similarly, histologic features of both cartilage and repaired tendons showed minimal differences across groups. Hence, in this rabbit model, a single injection of highly purified capsaicin into the GHJ does not induce a deleterious response with regard to cartilage matrix metabolism and cell viability, or rotator cuff healing. These data provide further evidence supporting the use of injectable, highly purified capsaicin as a safe alternative for management of postoperative pain following GHJ surgery. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1854–1860, 2015.     

The clinical profile of musculoskeletal injuries in children attending a major hospital in Delhi,India

Background

Children are vulnerable to musculoskeletal injuries both at home and on the street for various reasons. Morbidity and disabilities resulting from these, mostly preventable, injuries, make them a burden to their families and society. The role of various factors associated with injuries is often not documented.

Methods

This prospective study, done on 100 children aged up to 12 years with musculoskeletal trauma, analysed in details, the various modes of injuries.

Results

One in every five patient was a child below 12 years of age. Boys were injured more than girls. Injuries, especially fractures, were most common in the extremities, the upper limb more commonly injured than the lower limb. Most of the injuries occurred at home. The most common mode of injuries was falls that happened while playing both within and outside the home, followed by road traffic accidents. Most injuries occurred during daytime.

Conclusions

Injuries in children were found to be preventable. Small interventions while constructing homes can contribute tremendously to injury prevention and control in children. Parental awareness about the various modes of injury, role of supervised playing and their responsibility towards injury prevention can play a key role in reducing the morbidity associated with childhood fractures.     

Beard and Moustache Reconstruction

Beard and moustache reconstruction has gained more popularity and acceptance over the last decade. The procedure is done for the correction of facial areas with hair density deficit and also for the cosmetic enhancement of pre-existing facial hair. The surgical technique includes the harvesting of grafts from the scalp by the follicular unit excision (FUE) or follicular unit transplantation (FUT) technique and then placing them in either premade slits or by stick and place method. The advancement and refinement of procedure over the years has aided in achieving the optimal aesthetic results, with minimal side effects.     

Biallelic Pathogenic GFRA1 Variants Cause Autosomal Recessive Bilateral Renal Agenesis

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Serum cartilage oligomeric matrix protein (COMP) in knee osteoarthritis: A novel diagnostic and prognostic biomarker

A case–control study was conducted to estimate the association of cartilage oligomeric matrix protein (COMP) with knee osteoarthritis (OA) and to examine the potential utility of COMP as a diagnostic and prognostic biomarker in early knee OA. The COMP levels were estimated in the blood sera of 150 subjects belonging to study group (n = 100) and control one (n = 50). Patients with confirmed clinical isolated knee OA diagnosed through American College of Rheumatology criteria were included and were without any other cause of knee pain. ELISA was used to determine the levels of COMP, interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α). The median (range) serum COMP levels were observed to be 1117.21 ng/ml (125.03–4209.75 ng/ml) in OA patients and 338.62 ng/ml (118–589 ng/ml) in control subjects with p < 0.001. The COMP levels of study group were negatively correlated (correlation factor ?0.88) with disease duration and positively correlated with age, BMI, pain score and IL‐1β with correlation factors 0.86, 0.63, 0.76, and 0.79, respectively with p < 0.001. Gender differentiation was found in study group with 52% higher COMP level in males as compared to that of females. There was no significant correlation of COMP levels with radiological grading, erythrocyte sedimentation rate (ESR), hemoglobin (Hb), and TNF‐α. The serum COMP levels may be used as a diagnostic OA marker along with prognostic value in determining the patients at risk of rapidly progressing this debilitating joint disease. The serum COMP level remains significantly high in first 3 years of disease duration. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:999–1006, 2013

     

Ipsilateral rotational autokeratoplasty for the management of corneal opacities

PURPOSE/BACKGROUND: Penetrating keratoplasty is the logical solution for the management of corneal opacities. In situations such as in Papua New Guinea, where donor corneal tissue is scarce and corneal opacities are plenty, an alternative procedure for the management of corneal opacities in the form of ipsilateral rotational autokeratoplasty was considered. METHODS: In the present prospective study, ipsilateral rotational autokeratoplasty was performed in 17 eyes over a 2 year period in a general hospital.The patient's cornea was trephined eccentrically and the corneal opacity was dialed out of the visual axis and was replaced by clear peripheral cornea. RESULTS: Most opacities were leucomata (76.4%). The average size of the opacity was 5.1 mm and the corneal button size was 7 mm.A final visual acuity of 6/18 or better was obtained in 64.7% of cases (at 12 months). No significant postoperative complications were encountered. No complex formula was needed to calculate the size of the button and, by simply adding 3 mm to the pupillary diameter in standard illumination, one could make an estimation of the graft diameter. CONCLUSIONS: Rotational autokeratoplasty has a definite role in places where donor corneal tissue is scarce, in patients in whom long-term steroids are a risk or in situations where follow up of patients is difficult. Rejection is a theoretical impossibility, but late endothelial failure could occur, requiring regrafting. Rotational autokeratoplasty should be seriously considered as an alternative to conventional penetrating keratoplasty.     

Establishment of tyrosinase sequence database in normally pigmented Indians and Japanese for rapid determination of novel mutations

BACKGROUND: Many mutations of the tyrosinase gene have been reported in oculocutaneous albinism type I (OCA1) patient. In the future, a greater number of novel mutations will be found as the search for pathological mutations in the tyrosinase genes of OCA patients from various ethnic origins. For rapid determination in future whether an observed mutation is a polymorphism or a novel pathological one, sequence databases of the gene of various ethnic people are needed. OBJECTIVE: We established a sequence database of the tyrosinase gene of Japanese as well as Indian people. METHOD: We collected DNA from 109 Japanese and 103 Indians with normal pigmentation and analyzed their tyrosinase gene using a direct sequencing method. RESULT: The database shows an apparent difference between the two ethnic groups in polymorphisms of the tyrosinase gene namely, Q402 allele, Y192 allele and IV2+24 insT were found in the Indian population, but not in the Japanese. On the other hand, some Japanese had IV2-21 insT but none of the Indians did. The database supports the notion that the tyrosinase gene evolved and extended separately in the two ethnic groups. And the developing database confirmed that the reported mutations causing Indian and Japanese OCA were not among the polymorphisms in the database, which conversely gives genetical proof of the "genuine" pathological mutations. CONCLUSION: Eventually, the sequence database we established will contribute to demonstrating novel mutations of albinism in Indians and Japanese.