Twenty-four-hour oral tracer studies with L-[1-13C]lysine at a low (15 mg.kg (-1).d (-1) and intermediate (29 mg.kg (-1).d(-1)) lysine intake in healthy adults

BACKGROUND: We proposed previously that the mean lysine requirement value is approximately 30 mg * kg(-)(1) * d(-)(1) rather than the proposed 1985 FAO/WHO/UNU estimate of the upper range of the requirement, which is 12 mg * kg(-)(1) * d(-)(1). OBJECTIVE: Our objective was to explore the 24-h pattern and rate of whole-body lysine [l-(13)C]oxidation and status of whole-body lysine balance in healthy, young adults given an L-amino acid diet supplying either a low lysine intake (14-15 mg * kg(-)(1) * d(-)(1)) or an intermediate lysine intake (29 mg * kg(-)(1) * d(-)(1)) for 6 d before a continuous tracer study with L-[1-(13)C]lysine. DESIGN: Five subjects received the low lysine intake, 6 subjects received the intermediate intake, and all were studied by using a standard 24-h oral tracer protocol that was described earlier for studies at a generous lysine intake. RESULTS: The rate of lysine oxidation was not significantly different between the 12-h fasted and 12-h fed states. The daily oxidation rate (f1.gif" BORDER="0"> +/- SD) was 27. 9 +/- 8.8 and 27.3 +/- 17.6 mg lysine * kg(-)(1) * d(-)(1) for the low- and intermediate-intake groups, respectively (NS). Daily lysine balance was -12.4 +/- 92 and 1.8 +/- 17.7 mg * kg(-)(1) * d(-)(1), respectively (P < 0.025), for the low and intermediate intakes. The balance was significantly less than zero (P < 0.001) for the low intake. CONCLUSION: The FAO/WHO/UNU lysine requirement value is not sufficient to maintain lysine homeostasis in healthy adults. From the results of this and tracer studies done by others, the mean lysine requirement of healthy adults was determined to be 30 mg * kg(-)(1) * d(-)(1).     

Gut microbiota as a source of a surrogate antigen that triggers autoimmunity in an immune privileged site

Recent discoveries on the role of commensal microbiota have significantly changed our understanding of human physiology. The host-microbiota interplay is now an important aspect to take into account to understand immune responses and immunological diseases. Autoimmune uveitis is a sight-threatening disease that arises without a known infectious etiology. It is unknown where and how autoreactive T cells become primed to trigger disease in the eye, which is an immune privileged site. We recently reported data supporting the notion that retina-specific T cells receive a signal in the gut from commensal microbiota-derived cross-reactive antigen(s) and trigger autoimmune uveitis in the R161H mouse model. Here we discuss our published findings, as well as our recent attempts to identify the responsible microbe(s) by using different antibiotic treatments, 16S rDNA sequencing and homology searches for candidate antigenic mimic(s) of the retinal antigen.     

Balloon angioplasty and stenting of multiple intralobar pulmonary arterial stenoses in adult patients.

Balloon angioplasty and stent placement for pulmonary arterial stenoses in children are well-established therapies. In contrast, management of isolated peripheral pulmonary arterial stenoses in adults remains relatively unexplored. Four women (ages 18-63 years) with multiple discrete intralobar pulmonary arterial stenoses were treated with balloon angioplasty. Initially, 4-5 stenoses were dilated in each patient. The mean minimum diameter of the stenoses increased from 1.3 to 3.1 mm (P < 0.001), and the mean ratio of right ventricular to aortic systolic pressure decreased from 0.92 to 0.62 (P < 0.05). Each patient had marked symptomatic improvement. However, three patients developed recurrence of symptoms 4-24 months after angioplasty, and two had angiographic evidence of restenosis at previously dilated sites. These restenoses were treated with repeat angioplasty or stent implantation (three stents in each patient). One of these two patients developed near-occlusive restenosis of the stents and had successful bilateral lung transplantation. The other patient had a third catheterization with successful implantation of three additional stents. The third patient with recurrent symptoms died 2 years later, without further intervention. Transcutaneous catheter therapy for multiple intralobar pulmonary arterial stenoses in adults is highly successful acutely, but restenosis is common within several months. For some patients, balloon angioplasty and stent implantation may provide definitive management, while for others these procedures may serve as a bridge to lung transplantation.     

Low doses of cholestyramine in the treatment of hyperthyroidism

The enterohepatic circulation of thyroid hormones is increased in thyrotoxicosis. Bile-salt sequestrants bind thyroid hormones in the intestine and thereby increase their fecal excretion. Based on these observations, the use of cholestyramine has been tried. The present study evaluates the effect of low doses of cholestyramine as an adjunctive therapy in the management of hyperthyroidism. In a prospective, randomized, double-blind, placebo-controlled trial, 45 patients with newly diagnosed hyperthyroid Graves' disease were randomly assigned into the following treatment protocols: group I, cholestyramine 2 g BID, methimazole and propranolol; group II, cholestyramine 1 g BID, methimazole and propranolol; group III, placebo powder, methimazole and propranolol. The fixed dose of methimazole (30 mg/d) and propranolol (40 mg/d) was used. The study period was 4 weeks. Serum total triiodothyronine and free thyroxin were measured at baseline, and at the ends of the second and the fourth week of the study. The serum thyroid hormone levels decreased more rapidly and to a greater extent in the cholestyramine-treated groups. All of the patients in group I had achieved euthyroid state at the end of the study. We conclude that low dose of cholestyramine is an effective and well-tolerated adjunctive agent in the treatment of hyperthyroid Graves' disease.     

Persistent Truncus Arteriosus With Intact Ventricular Septum: Clinical,Hemodynamic and Short-term Surgical Outcome

Introduction:

Truncus arteriosus with intact ventricular septum is a rare and unique variant of persistent truncus arteriosus (PTA) which usually presents with central cyanosis and congestive heart failure in neonate and early infancy. Associated cardiac and non-cardiac anomalies may affect morbidity and mortality of these patients.

Case Presentation:

We describe clinical presentation, echocardiography and angiographic features of a 7-month old boy with PTA and intact ventricular septum who underwent surgical repair of the anomaly at our institution. Operative findings, surgical procedure and short-term outcome are reported.

Conclusions:

While our patient had systemic pulmonary arterial pressure at the time of complete surgical repair, it was improved after surgery.     

CCR5 Δ 32 mutation is not prevalent in Iranians with chronic HBV infection

CCR5 is an important chemokine receptor involved in the recruitment of specific anti‐viral immune cells (e.g., NK cells and T cytotoxic cells) to the liver. Previous studies indicated that the Δ 32 mutation in CCR5 gene led to inactivation of CCR5. Several conflicting studies have suggested that this mutation may be associated with either recovery or persistence of HBV infection. The main purpose of this study was to compare the frequency of the Δ 32 mutation within the CCR5 gene in a group of patients infected chronically with HBV with healthy individuals from South‐East of Iran. Sixty patients with chronic HBV infection as well as 300 age‐, and sex‐match healthy individuals were enrolled in this study. Gap‐PCR was applied to determine the frequency of CCR5 Δ 32 mutation in both groups. The results demonstrated that none of the patients infected with HBV carried the CCR5 Δ 32 mutation while, 3 (1%) of the healthy individuals were found to be heterozygotic for this mutation. The CCR5 Δ 32 mutation is not a prevalent mutation in either the patients infected chronically with HBV or their health counterparts in the South‐East region of Iran. This may be attributed to either different genetic settings of the investigated population or lack of any significant correlation between this mutation and HBV pathogenicity. J. Med. Virol. 85: 964–968, 2013. © 2013 Wiley Periodicals, Inc.     

Clinical Presentation and Management of Severe Acute Renal Failure in McArdle Disease

McArdle disease, also known as glycogen storage disease type V, is an autosomal recessive disease due to the absence of myophosphorylase activity, leading to the complete disruption of glycogen breakdown in muscles. We present a rare case of a Caucasian male, aged 26 years, who developed rhabdomyolysis-induced acute renal failure and uremic encephalopathy. Neurological examination and histopathological studies supported the diagnosis of McArdle disease. The severity of his symptoms necessitated urgent hemodialysis, upon which the patient reported improvement in status. Acute renal failure in McArdle disease usually resolves with supportive treatment and maintenance of regular physical activity. Nevertheless, in more severe cases, intensive care with urgent hemodialysis may be needed. A multidisciplinary approach is necessary for the adequate management of similar cases.     

Identifying and prioritizing industry-level competitiveness factors: evidence from pharmaceutical market

Background

Pharmaceutical industry is knowledge-intensive and highly globalized, in both developed and developing countries. On the other hand, if companies want to survive, they should be able to compete well in both domestic and international markets. The main purpose of this paper is therefore to develop and prioritize key factors affecting companies’ competitiveness in pharmaceutical industry. Based on an extensive literature review, a valid and reliable questionnaire was designed, which was later filled up by participants from the industry. To prioritize the key factors, we used the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS).

Results

The results revealed that human capital and macro-level policies were two key factors placed at the highest rank in respect of their effects on the competitiveness considering the industry-level in pharmaceutical area.

Conclusion

This study provides fundamental evidence for policymakers and managers in pharma context to enable them formulating better polices to be proactively competitive and responsive to the markets’ needs.