Effect of a resistance exercise at acute moderate altitude on muscle health biomarkers.

The intensification of the stress response during resistance training (RT) under hypoxia conditions could trigger unwanted effects that compromise muscle health and, therefore, the ability of the muscle to adapt to longer training periods. We examined the effect of acute moderate terrestrial hypoxia on metabolic, inflammation, antioxidant capacity and muscle atrophy biomarkers after a single RT session in a young male population. Twenty healthy volunteers allocated to the normoxia (N < 700 m asl) or moderate altitude (HH = 2320 m asl) group participated in this study. Before and throughout the 30 min following the RT session (3 × 10 reps, 90 s rest, 70% 1RM), venous blood samples were taken and analysed for circulating calcium, inorganic phosphate, cytokines (IL-6, IL-10 and TNF-α), total antioxidant capacity (TAC) and myostatin. Main results displayed a marked metabolic stress response after the RT in both conditions. A large to very large proportional increase in the adjusted to pre-exercise change of inflammatory and anti-inflammatory markers favoured HH (serum TNF-α [ES = 1.10; p = 0.024] and IL-10 [ES = 1.31; p = 0.009]). The exercise produced a similar moderate increment of myostatin in both groups, followed by a moderate non-significant reduction in HH throughout the recovery (ES = - 0.72; p = 0.21). The RT slightly increased the antioxidant response regardless of the environmental condition. These results revealed no clear impact of RT under acute hypoxia on the metabolic, TAC and muscle atrophy biomarkers. However, a coordinated pro/anti-inflammatory response balances the potentiated effect of RT on systemic inflammation.

Subcutaneous granuloma annulare induced by acetazolamide.

A 9-year-old boy presented with recurring subcutaneous nodules on both legs and knees temporally related each time to acetazolamide treatment for idiopathic intracranial hypertension. A biopsy of one of the lesions revealed palisaded granulomas in the hypodermis around necrobiotic collagen and interstitial accumulation of mucin, compatible with subcutaneous granuloma annulare (SGA). To the best of our knowledge, this is the first case that establishes an association between SGA and acetazolamide.

Foamy Virus Vectors Transduce Visceral Organs and Hippocampal Structures following In Vivo Delivery to Neonatal Mice.

Viral vectors are rapidly being developed for a range of applications in research and gene therapy. Prototype foamy virus (PFV) vectors have been described for gene therapy, although their use has mainly been restricted to ex vivo stem cell modification. Here we report direct in vivo transgene delivery with PFV vectors carrying reporter gene constructs. In our investigations, systemic PFV vector delivery to neonatal mice gave transgene expression in the heart, xiphisternum, liver, pancreas, and gut, whereas intracranial administration produced brain expression until animals were euthanized 49 days post-transduction. Immunostaining and confocal microscopy analysis of injected brains showed that transgene expression was highly localized to hippocampal architecture despite vector delivery being administered to the lateral ventricle. This was compared with intracranial biodistribution of lentiviral vectors and adeno-associated virus vectors, which gave a broad, non-specific spread through the neonatal mouse brain without regional localization, even when administered at lower copy numbers. Our work demonstrates that PFV can be used for neonatal gene delivery with an intracranial expression profile that localizes to hippocampal neurons, potentially because of the mitotic status of the targeted cells, which could be of use for research applications and gene therapy of neurological disorders.

Port-wine stain as a clue for two rare coexisting entities.

Phakomatosis pigmentovascularis (PPV) is an uncommon dermatosis characterised by the presence of both pigmentary and vascular abnormalities.1 Its pathogenesis is not elucidated, and the prognosis is mainly determined by the presence of extracutaneous manifestations, such as Klippel-Trenaunay syndrome (KTS), that is defined by the triad of a port-wine stain (PWS), anomalous veins and progressive overgrowth of the affected extremity. Herein, we report a case of an adult patient, who presented with a large PWS, nevus of Ota, ocular melanosis, and limb hypertrophy and varicosities. These findings represented a rare association of PPV type IIb and KTS.

Cutaneous nocardiosis by a new pathogenic species: Nocardia grenadensis.

Nocardiosis is a rare, predominantly opportunistic, suppurative disease caused by bacteria of the order Actinomycetales. There are currently more than 100 species of Nocardia described, less than half are pathogenic to humans. Cutaneous nocardiosis can be caused by direct inoculation from a contaminated material or by secondary dissemination. The authors present a 70-year-old man with an autoimmune haemolytic anaemia treated with prednisolone and azathioprine. The patient presented multiple erythematous tender nodules with linear distribution and proximal progression along the left upper limb with 2 months of evolution. The skin biopsy revealed non-specific inflammation with areas of abscess. Culture was positive for bacteria of the genus Nocardia, and molecular techniques revealed Nocardia grenadensis The patient was treated with minocycline with good response, but the disease recurred. N. grenadensis was first identified in 2012 in a bioprospecting process. The authors now describe the first case of cutaneous nocardiosis caused by N. grenadensis.

Reed's Syndrome.

Multiple cutaneous and uterine leiomyomatosis (MCUL), also known as Reed's syndrome, is a rare genodermatosis, with an autosomal dominant pattern of inheritance. It results from a germline heterozygous mutation of fumarate hydratase gene, that is classified as a tumor suppressor gene. Hereditary leiomyomatosis and renal cell cancer is characterized by the association of MCUL with renal cell carcinoma. We report a case of a 57-year-old woman, with multiple cutaneous leiomyomas as the presenting sign of Reed's syndrome.

Pulmonary Embolism and Intracardiac Type A Thrombus with an Unexpected Outcome.

Detection of right heart thrombi (RHT) in the context of pulmonary thromboembolism (PE) is uncommon (4-18%) and increases the risk of mortality beyond the presence of PE alone. Type A thrombi are serpiginous and highly mobile and are thought to be originated from large veins and captured in-transit within the right heart. Optimal management of RHT is still uncertain. A 79-year-old woman, with a history of recent total hysterectomy with adnexectomy and a Wells procedure, presented to the emergency department following an episode of syncope. Computed tomography revealed bilateral PE and the presence of a right atrial thrombus. Transthoracic echocardiography demonstrated a free-floating type A thrombus in the right atrium, protruding into the right ventricle, and signs of pulmonary hypertension and right ventricle dysfunction. Considering the recent surgery and clinical stability, treatment with heparin alone was decided. Subsequent clinical improvement was observed and echocardiographic follow-up revealed complete thrombus dissolution and complete recovery of right ventricle function. Most authors recommend treatment of PE with RHT with thrombolysis or embolectomy followed by anticoagulation, although evidence is scarce. Individual risk of hemorrhage and operatory-related mortality should be taken into account when defining the treatment strategy especially when benefit is not firmly established.

Cat eye syndrome and growth hormone deficiency with pituitary anomalies: a case report and review of the literature.

Cat eye syndrome is a rare congenital disease characterized by the existence of a supernumerary chromosome derived from chromosome 22, with a variable phenotype comprising anal atresia, coloboma of the iris and preauricular tags or pits. We report a girl with cat eye syndrome, presenting short stature, with growth hormone deficiency due to posterior pituitary ectopia. Short stature is a common feature of this syndrome, and the association with a structural pituitary anomaly has been described, however growth hormone deficiency and the underlying mechanisms are rarely reported. A review on short stature and growth hormone deficiency in cat eye syndrome is conducted.

Pyridoxamine reverts methylglyoxal-induced impairment of survival pathways during heart ischemia.

BACKGROUND AND AIMS: Increased levels of advanced glycation end-products (AGE) and their precursors, such as methylglyoxal (MG), in patients with diabetes may account for impaired response to heart ischemia. Pyridoxamine is a derivate of vitamin B6, which has been shown to reduce AGE formation. Our goal was to assess the role of pyridoxamine in protecting from MG-induced impaired heart response to ischemia. METHODS: Wistar rats were subjected to MG administration (WM), MG plus pyridoxamine (WMPyr), or no treatment (W). Half of the hearts from each group were submitted to ischemia and the other half were perfused as control. The levels of CEL, Bcl-2, Bax, and total and phosphorylated forms of JNK and Akt were determined. RESULTS: Methylglyoxal led to higher levels of AGE and AGE receptor (RAGE) than in the W group. During ischemia, MG caused an impairment of survival pathways and Bcl-2/Bax ratio, a marker of apoptosis. Pyridoxamine treatment decreased glycation and restored the activation of JNK and Akt during ischemia. These events were followed by levels of Bcl-2/Bax ratio similar to W group. CONCLUSION: Methylglyoxal-induced AGE accumulation impairs the activation of cell survival pathways during ischemia. Pyridoxamine-induced decrease of glycation inhibited the effects of MG accumulation in the heart, suggesting that it can be of added value to usual diabetic therapy.

Cerebral embolism from Libman-Sacks endocarditis.

Libman-Sacks endocarditis consists of aseptic valvular abnormalities, associated with systemic lupus erythematosus and antiphospholipid syndrome. Embolic ischaemic stroke is a possible clinical presentation. The authors present the case of a woman in her fourth decade who developed central facial palsy after several transient ischaemic attacks with visual loss. Cerebral imaging revealed multiple small ischaemic lesions in the right hemisphere. The transoesophagic echocardiogram showed mitral vegetations and she tested positive for antiphospholipid antibodies. She underwent mitral valve replacement for a mechanical prosthesis due to extensive valvular damage and started anticoagulation. The valve's microbiological exams were negative establishing the diagnosis of libman-sacks endocarditis. Endocarditis should be suspected with sequential cerebral ischaemia in patients of all ages. Valvular surgery is the mainstay of treatment in recurrent embolic events. Association with antiphospholipid antibodies is common yet a poor-known fact. The patient is currently asymptomatic on warfarin and aspirin, with a normal functioning mitral prosthesis.