Volume and Infusion Rate Dynamics of Intraparenchymal Central Nervous System Infusion in a Large Animal Model.

Thalamic infusion of adeno-associated viral (AAV) vectors has been shown to have therapeutic effects in neuronopathic lysosomal storage diseases. Preclinical studies in sheep model of Tay-Sachs disease demonstrated that bilateral thalamic injections of AAV gene therapy are required for maximal benefit. Translation of thalamic injection to patients carries risks in that (1) it has never been done in humans, and (2) dosing scale-up based on brain weight from animals to humans requires injection of larger volumes. To increase the safety margin of this infusion, a flexible cannula was selected to enable simultaneous bilateral thalamic infusion in infants while monitoring by imaging and/or to enable awake infusions for injection of large volumes at low infusion rates. In this study, we tested various infusion volumes (200-800 µL) and rates (0.5-5 µL/min) to determine the maximum tolerated combination of injection parameters. Animals were followed for ∼1 month postinjection with magnetic resonance imaging (MRI) performed at 14 and 28 days. T1-weighted MRI was used to quantify thalamic damage followed by histopathological assessment of the brain. Trends in data show that infusion volumes of 800 µL (2 × the volume required in sheep based on thalamic size) resulted in larger lesions than lower volumes, where the long infusion times (between 13 and 26 h) could have contributed to the generation of larger lesions. The target volume (400 µL, projected to be sufficient to cover most of the sheep thalamus) created the smallest lesion size. Cannula placement alone did result in damage, but this is likely associated with an inherent limitation of its use in a small brain due to the length of the distal rigid portion and lack of stable fixation. An injection rate of 5 µL/min at a volume ∼1/3 of the thalamus (400-600 µL) appears to be well tolerated in sheep both clinically and histopathologically.

Jaundice, phototherapy and DNA damage in full-term neonates.

OBJECTIVE: Phototherapy is the standard therapeutic approach for neonatal hyperbilirubinemia. Oxidative effects of phototherapy may have potential harms, including DNA damage. Unconjugated bilirubin (UCB) might also possess antigenotoxic potential. Intensive phototherapy is more efficacious than conventional phototherapy in treating hyperbilirubinemia. This study aimed to assess the impact of hyperbilirubinemia and the two different types of phototherapy on DNA damage in peripheral blood mononuclear cells of neonates. STUDY DESIGN: The study was conducted on term neonates with non-hemolytic hyperbilirubinemia and control healthy neonates. Genotoxicity was assessed using single-cell gel electrophoresis (Comet assay) in peripheral mononuclear cells. Blood samples were obtained at enrollment in all infants and after intensive or conventional phototherapy in jaundiced infants. RESULT: DNA damage did not significantly differ between jaundiced and non-jaundiced neonates (11.4±8.7 and 10.9±8.3 arbitrary units (AU), respectively, P=0.58). It increased significantly after exposure to phototherapy compared with prephototherapy values (45.6±14.7 vs 11.4±8.7 AU, respectively, P<0.001). The duration of phototherapy correlated positively with markers of DNA damage (r=0.86, P<0.001); however, the intensity of used light did not significantly impact genotoxicity. CONCLUSION: Hyperbilirubinemia does not influence DNA damage, whereas both conventional and intensive phototherapy are associated with DNA damage in term infants with hyperbilirubinemia.

Estimation of resveratrol content in peanut pericarp and its relation to the in vitro inhibitory activity on carbohydrate metabolizing enzymes.

The aim of this work was the estimation of resveratrol content in two successive extracts (EtOAc and MeOH) of peanuts (Arachis hypogaea L.) pericarp of Egypt, by TLC and HPLC methods. Results showed the presence of 3.0 and 0.5 microg/mL resveratrol in EtOAc and MeOH extracts respectively. The in vitro carbohydrate hydrolyzing enzyme inhibition activity showed higher percentage of inhibition of alpha-amylase, alpha-glucosidase and beta-galactosidase with EtOAc (4.32, 5.93 and 13.7%) than with MeOH extract (3.9, 4.9 and 14.1%) but lower than the standard resveratrol concentration (5.18, 5.94 and 13.26%) and the reference acarbose (5.88, 5.9 and 13.0%). It could be concluded that the content of resveratrol in peanut pericarp is related to the percentage of inhibition activity of carbohydrate hydrolyzing enzymes. These results strongly reflect the benefit of using peanut pericarp, the waste product, as a natural antidiabetic agent.

Antioxidant and schistosomicidal effect of Allium sativum and Allium cepa against Schistosoma mansoni different stages.

OBJECTIVE: The schistosomicidal properties of garlic (Allium sativum) and onion (Allium cepa) powder were tested in vitro against Schistosoma mansoni miracidia, schistosomula, cercaria and adult worms. Results indicate their strong biocidal effects against all stages of the parasite and also show scavenging inhibitory effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO). MATERIALS AND METHODS: In the present work, the in vivo effects of A. sativum and A. cepa on lipid peroxide and some antioxidant enzymes; thioredoxin reductase (TrxR), sorbitol dehydrogenase (SDH), superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) (as they have a crucial role in host protection against invading parasite) were also studied. RESULTS: The data demonstrate that, there was a significant inhibition in SOD, CAT, GR, TrxR and SDH in infected liver while, significant elevation was detected in lipid peroxide as compared to the normal control. The current resultS clearly revealed that, the used both edible plants enhance the host antioxidant system indicated by lowering in lipid peroxide and stimulation of SOD, CAT, GR, TrxR and SDH enzyme levels. CONCLUSIONS: Enhancement of such enzymes using A. sativum and A. cepa could in turn render the parasite vulnerable to damage by the host and may play a role in the antischistosomal potency of the used food ingredients.

Comparative effects of zinc, selenium and vitamin E or their combination on carbohydrate metabolizing enzymes and oxidative stress in streptozotocin induced-diabetic rats.

OBJECTIVE: It is well documented that oxidative stress is a basic mechanism behind the development of diabetic state. The current study was undertaken to elucidate the hypoglycemic role of zinc, selenium and vitamin E and their mixture in comparison with the antidiabetic drug glibenclamide. MATERIALS AND METHODS: Male Wistar rats weighing 250 +/- 50 g were made diabetic by injection with a single i.p. dose of streptozotocin (STZ) (65 mg/kg b. wt). Diabetic groups were simultaneously i.p. injected either with zinc chloride (ZnCI2) (5 mg/kg) or with selenium and vitamin E (1.5 mg/kg as sodium selenite and vitamin E 1000 mg/kg) or with zinc, selenium and vitamin E each element i.p. injected according to its corresponding therapeutic dose daily for one month. Another group was orally treated daily with glibenclamide drug (5 mg/kg) for one month. RESULTS: Blood and tissue samples were collected at day 3 post STZ injection (from one group serum glucose level significantly elevated < or = 300, p < or = 0.05) and at day 30 post-treatment in other groups. Liver function, nitric oxide (NO), malondialdehyde (MDA) and phosphoenol pyruvate carboxykinase (PEPCK) were significantly increased, while superoxide dismutase (SOD), reduced glutathione (GSH), total protein, lactate dehydrogenase (LDH), pyruvate kinase (PK) and hexokinase (HK) were inhibited after STZ treatment. Histological examination of diabetic liver showed necrosis and degenerative changes of hepatocytes. Treatment of diabetic rats with ZnCI2, selenium and vitamin E or their combination blunted the increment in serum glucose induced by STZ, preserved liver architecture and ameliorated all the previous mentioned biochemical parameters. CONCLUSIONS: It was found that, the combined administration of zinc, selenium and vitamin E exhibited a more remarkable effect than either zinc or selenium and vitamin E. So, the results clearly indicate the beneficial effects of micronutrients combination in controlling hyperglycemia.

Massage with kinesthetic stimulation improves weight gain in preterm infants.

OBJECTIVE: The aim of this study was to evaluate the effects of massage with or without kinesthetic stimulation on weight gain and length of hospital stay in the preterm infant. STUDY DESIGN: A prospective randomized clinical trial was conducted evaluating the effects of massage with or without kinesthetic stimulation (KS) on weight gain and length of stay (LOS) in medically stable premature (<1500 g and/or and <1000 g) was also performed. RESULT: A total of 60 premature infants were recruited for this study; 20 infants in each group. Average daily weight gain and LOS were similar between the groups after controlling for covariates. For infants with BW>1000 g, average daily weight gain was increased in the intervention groups compared to control. This effect was mainly attributable to the M/KS group. CONCLUSION: Massage with KS is a relatively simple and inexpensive intervention that can improve weight gain in selected preterm infants. Length of hospital stay is not impacted by massage with or without KS. Further studies are needed to evaluate the effect of massage in the extremely low BW(<1000 g) infant.

Morbid hypocalcemia associated with phosphate enema in a six-week-old infant.

A 6-week-old premature infant who was born at 29 weeks of gestation presented to the emergency department with a several-hour history of stiffness and increased alarms on his apnea monitor at home. On arrival he was noted to have generalized seizures, apnea, and bradycardia. He was intubated and required cardiopulmonary resuscitation including chest compressions and medications. After stabilization he was transferred to the neonatal intensive care unit for further management. His initial laboratory tests revealed a serum calcium level of 2.4 mg/dL (normal range: 8.4-10.2 mg/dL) and a serum phosphorus level of 28.5 mg/dL (normal range: 2.4-4.5 mg/dL). During the first week of admission, the infant's mother reported that she had administered a full pediatric Fleets enema (CB Fleet Company Inc, Lynchburg, VA) to him. The infant was discharged after 12 days of hospitalization. Anticipatory guidance on the stool patterns and behavior of infants can prevent misconceptions about constipation that are especially prevalent in new parents. Proper management of constipation, should it arise, should be addressed with all parents at early well-child visits to avoid hazardous complications of treatments. hypocalcemia, seizures, premature infants, enema.