Nutrition and management of glycemia in neonates with neonatal encephalopathy treated with hypothermia.

Adequate nutrition and glycemic homeostasis are increasingly recognized as potentially neuroprotective for the developing brain. In the context of hypoxia-ischemia, evidence is scarce regarding optimal nutritional support and administration route, as well as the short- and long-term consequences of such interventions. In this review, we summarize current knowledge on disturbances of brain metabolism of glucose and substrates by hypoxia-ischemia, and compound effects of these mechanisms on brain injury characterized by specific patterns on EEG and MRI. Risks and benefits of nutrition delivery via parenteral or enteral routes are examined. Nutrition could mitigate adverse neurodevelopmental outcomes, and the impact of nutritional strategies and specific nutritional interventions are reviewed. Limited literature highlights the need for further studies to understand the changes in energy metabolism during and after hypoxic-ischemic injury, to optimize nutritional regimens and glucose management, and to inform the neuroprotective role of nutrition.

Brain injury patterns in hypoglycemia in neonatal encephalopathy.

BACKGROUND AND PURPOSE: Low glucose values are often seen in term infants with NE, including HIE, yet the contribution of hypoglycemia to the pattern of neurologic injury remains unclear. We hypothesized that MR features of neonatal hypoglycemia could be detected, superimposed on the predominant HIE injury pattern. MATERIALS AND METHODS: Term neonates (n = 179) with NE were prospectively imaged with day-3 MR studies and had glucose data available for review. The predominant imaging pattern of HIE was recorded as watershed, basal ganglia, total, focal-multifocal, or no injury. Radiologic hypoglycemia was diagnosed on the basis of selective edema in the posterior white matter, pulvinar, and anterior medial thalamic nuclei. Clinical charts were reviewed for evidence of NE, HIE, and hypoglycemia (<46 mg/dL). RESULTS: The predominant pattern of HIE injury imaged included 17 watershed, 25 basal ganglia, 10 total, 42 focal-multifocal, and 85 cases of no injury. A radiologic diagnosis of hypoglycemia was made in 34 cases. Compared with laboratory-confirmed hypoglycemia, MR findings had a positive predictive value of 82% and negative predictive value of 78%. Sixty (34%) neonates had clinical hypoglycemia before MR imaging. Adjusting for 5-minute Apgar scores and umbilical artery pH with logistic regression, clinical hypoglycemia was associated with a 17.6-fold higher odds of MR imaging identification (P < .001). Selective posterior white matter and pulvinar edema were most predictive of clinical hypoglycemia, and no injury (36%) or a watershed (32%) pattern of injury was seen more often in severe hypoglycemia. CONCLUSIONS: In term infants with NE and hypoglycemia, specific imaging features for both hypoglycemia and hypoxia-ischemia can be identified.

Opposing responses of apoptosis and autophagy to moderate compression in skeletal muscle.

AIM: The molecular mechanism that contributes to the pathogenesis of deep pressure ulcer remains to be elucidated. This study tested the hypotheses that: (1) apoptosis and autophagy are activated in compression-induced muscle pathology and (2) apoptotic and autophagic changes precede pathohistological changes in skeletal muscle in response to prolonged moderate compression. METHODS: Adult Sprague-Dawley rats were subjected to an experimental model of pressure-induced deep tissue injury. Static pressure of 100 mmHg was applied to an area of 1.5 cm(2) over the mid-tibialis region of right limb of rats for one single session of 6-h compression (1D) or two sessions of 6-h compression over two consecutive days with rats sacrificed one day (2D) or immediately after (2D-IM) the compression. The left uncompressed limb served as the intra-animal control. Muscle tissues underneath compression region were collected for analysis. RESULTS: Our histological analysis indicated that pathohistological characteristics including rounding contour of myofibres and massive nuclei accumulation were apparently demonstrated in muscles of 2D and 2D-IM. In contrast, these pathohistological changes were generally not found in muscle following 1D. Apoptotic DNA fragmentation, terminal dUTP nick-end labelling index and caspase-3 protease activity were significantly elevated in compressed muscles of all groups. Caspase-9 enzymatic activity was found to be significantly increased in compressed muscles of 2D and 2D-IM whereas increase in caspase-8 activity was exclusively found in compressed muscle of 1D. According to our immunoblot analysis, FoxO3 was significantly reduced in compressed muscles of all groups whereas Beclin-1 was decreased only in 2D. LC3-I was significantly reduced in compressed muscles of all groups while LC3-II was decreased in 2D and 1D. No significant differences were found in the protein abundance of Akt and phospho-Akt in muscles among all groups. CONCLUSION: These data demonstrate the opposing responses of apoptosis and autophagy to moderate compression in muscle. Moreover, our findings suggest that cellular changes in apoptosis and autophagy have already taken place in the very early stage in which apparent histopathology has yet to develop in the process of compression-induced muscle pathology.

A novel mitochondrial DNA mutation in COX1 leads to strokes, seizures, and lactic acidosis.

Cytochrome c oxidase (COX) is the terminal enzyme of the respiratory chain, with subunits originating both from the mitochondrial and nuclear genome. An eleven-year-old female presented initially with a seizure followed two months later with tonic-clonic seizures, weakness and aphasia. MRI of the cerebral hemispheres showed multiple infarcts. Previous history suggested gross and fine motor control deficits with learning difficulties. A muscle biopsy showed a specific decrease of COX staining in all fibres and pleomorphic mitochondria. Respiratory chain studies confirmed an isolated complex IV defect in muscle, whilst fibroblasts showed an initial COX activity below normal which rapidly came up to the normal range on culture. Sequencing of mtDNA revealed an heteroplasmic m.7023G>A mutation in the COX1 gene, with levels of 96% in muscle, 70% in blood and 50% in the initial skin fibroblast culture dropping to 10% in later passages. The mutation was present in a critical region of the COX1 gene, the V374M change being close to the two histidine residues His376 and His378 co-ordinating with the heme a and a (3), and His367 which co-ordinates a magnesium ion. This case highlights that a MELAS-like syndrome can occur with isolated COX deficiency.

Testicular atrophy in therapeutic orchiectomy specimens from men with prostate carcinoma: association with prior prostate bed radiation and older age.

BACKGROUND: The significance of testicular atrophy at the time of therapeutic orchiectomy for prostate carcinoma has not been examined even though hypogonadism may occur after prostate bed radiation therapy for these tumors, may itself be symptomatic, and also may be associated with poor tumor prognosis. METHODS: Therapeutic orchiectomy specimens from 78 men with prostate carcinoma and no preceding hormonal therapy were evaluated histologically for atrophy. Observations were related to prior radiation therapy, tumor grade and stage diagnosis, host age, obesity, and smoking habits. RESULTS: Thirty-five men who previously received radiation therapy to the prostate bed had testicular atrophy more frequently than 43 men without prior radiation (71% vs. 28%) (P < 0.001). In men without prior radiation, atrophy was less common in specimens from those age < 70 years than in specimens from men age > 70 years (7% vs. 38%) (P < 0.04). In men with prior radiation, prominent atrophy occurred with similar frequency in specimens from both younger and older men, and was more frequent in specimens obtained within 3 years after radiation therapy than in specimens obtained after longer postradiation intervals (89% vs. 53%) (P < 0.001). CONCLUSIONS: Testicular atrophy at the time of therapeutic orchiectomy for men with prostate carcinoma is much more common in patients with prior prostate bed radiation therapy. Available evidence suggests that this association may reflect both radiation-induced testicular injury and more frequent early tumor recurrence in men with atrophy preceding their radiation therapy.