Stereotaxic Administration of 1-Methyl-4-Phenylpyridinium Ion (MPP+) Decreases Striatal Fructose 2,6-Bisphosphate in Rats

Abstract: The Stereotaxic administration of 1-methyl-4-phenylpyridinium ion (MPP⁺) into the neostriatum of male rats caused a lesion that resulted in a large dose-dependent loss of striatal fructose 2,6-bisphosphate; initial values were restored 5 days after the treatment. This effect was not protected by systemic administration of MK-801 or by nitroarginine. The content of hexose 6-phosphates and ATP was also reduced by MPP⁺ treatment, whereas lactate was increased. Biochemical and histological results suggested that MPP⁺ caused a nonselective cell death, followed by a pronounced astroglial response, parallel to fructose 2, 6-bisphosphate recovery. The Stereotaxic administration of rotenone showed a different time effect on fructose 2,6-bisphosphate cerebral content, with a significantly faster recovery. These results indicate that cerebral fructose 2,6-bisphosphate may be a sensitive metabolite related to brain damage caused by potent neurotoxins such as MPP⁺. On the other hand, they show that MPP⁺ acts in the brain through a quick, strong cytotoxic mechanism, which probably involves mechanisms other than mitochondria! chain blockage     

Cardiovascular risk reduction over time in patients with diabetes or pre-diabetes undergoing bariatric surgery: data from a single-center retrospective observational study

Background

Bariatric surgery is effective in remission of obesity comorbidities. This study was aimed at comparing CVD risk between morbidly obese patients with type 2 diabetes and pre-diabetes before and after bariatric surgery as well as assessing comorbidities.

Methods

This is a retrospective observational study with 105 patients with type 2 diabetes (DMbaseline) and prediabetes (preDMbaseline) who underwent Roux-en-Y gastric bypass. Data were collected preoperative and then at 3,6,12,18,24,36,48, and 60?months after surgery. Anthropometric, cardiovascular and glycemic parameters were assessed. CVD risk was calculated using the Framingham Risk Score.

Results

Prior to surgery, 48 patients had type 2 diabetes, while 57 had pre-diabetes. Mean age was 48 (9.2) and mean BMI was 52 (7.4). 26.1% of patients had a high CVD risk. CVD risk decreased in patients with type 2 diabetes and prediabetes at month 12 after surgery compared to the baseline risk (p?<?0.001). BMI, body fat percentage, fasting plasma glucose, HbA1c, c-peptide, HOMA-IR, LDL-c, systolic blood pressure, and diastolic blood pressure decreased during the first year after surgery. From the 12th month until the 60th, they showed a flat trend, or a very mild increase in some cases. 3.2% of patients maintained high CVD risk at 60?months. Type 2 diabetes remission was 92%. No patient of the preDMbaseline group developed type 2 diabetes.

Conclusion

Bariatric surgery reduces CVD risk in type 2 diabetes and pre-diabetes. Given that patients with type 2 diabetes benefit the most, more studies are necessary to consider pre-diabetes as a criterion for metabolic surgery in patients with BMI?≥?35?kg/m².

     

Body condition and feather molt of a migratory shorebird during the non‐breeding season

Migratory shorebirds have some of the highest fat loads among birds, especially species which migrate long distances. The upland sandpiper Bartramia longicauda makes long‐distance migrations twice a year, but variation in body condition or timing of feather molt during the non‐breeding season has not been studied. Molt is an important part of the annual cycle of migratory birds because feather condition determines flight performance during migration, and long‐distance movements are energetically costly. However, variation in body condition during molt has been poorly studied. The objective of our field study was to examine the timing and patterns of feather molt of a long distance migratory shorebird during the non‐breeding season and test for relationships with body size, fat depots, mass, and sex. Field work was conducted at four ranches in the Northern Campos of Uruguay (Paysandú and Salto Departments). We captured and marked 62 sandpipers in a 2‐month period (Nov–Jan) during four non‐breeding seasons (2008–2012). Sex was determined by genetic analyses of blood samples taken at capture. Molt was measured in captured birds using rank scores based on published standards. Body mass and tarsus length measurements showed female‐biased sexual size dimorphism with males smaller than females. Size‐corrected body mass (body condition) showed a U‐shaped relationship with the day of the season, indicating that birds arrived at non‐breeding grounds in relatively good condition. Arriving in good body condition at non‐breeding grounds is probably important because of the energetic demands due to physiological adjustments after migration and the costs of feather molt.     

Tissue-specific activation of the osmotin gene by ABA,C2H4 and NaCl involves the same promoter region

The gene encoding the antifungal protein osmotin is induced by several hormonal and environmental signals. In this study, tissue-specific and inducer-mediated expression of the reporter gene -glucuronidase (uidA) fused to different fragment lengths of the osmotin promoter was evaluated in transgenic tobacco (Nicotiana tabacum). The region of the promoter between –248 to –108 (Fragment A) was found to be essential and sufficient for inducer (abscisic acid (ABA), C₂H₄ and NaCl)-mediated expression of the reporter gene. Expression of the reporter gene was developmentally regulated and increased with maturity of leaves, stem and flowers. Expression also was tissue-specific being most highly expressed in epidermis and vascular parenchyma of the stem. The regulators ABA, C₂H₄ and NaCl exhibited tissue-specific induction of this promoter. The promoter was specifically responsive to C₂H₄ in flowers at virtually all stages of development, but not responsive in these tissues to ABA or NaCl. Conversely, ABA and NaCl were able to induce reporter gene activity using promoter Fragment A in specific tissues of root where C₂H₄ was unable to induce activity. Further dissection of the promoter Fragment A into fragments containing either the conserved GCC element (PR); PR/AT; or G/AT sequences, and subsequent testing of these fragments fused to GUS in transgenic plants was performed. These experiments revealed that the promoter fragment containing PR element alone, although required, was barely able to allow responsiveness to C₂H₄. However, significant C₂H₄-induced activity was obtained with a promoter fragment containing the AT and PR elements together.     

Large quantities of recombinant PR-5 proteins from the extracellular matrix of tobacco: Rapid production of microbial-recalcitrant proteins

A procedure for the extraction of large quantities of PR-5 proteins that have been recalcitrant to microbial-based expression systems is described. Targeting of the recombinant proteins to the extracellular matrix allowed efficient protein extraction by a vacuum infiltration/centrifugation system. Approximately 1 kg of fresh leaves from transgenic tobacco plants overexpressing either truncated osmotin (Liu et al., 1996) or A9 fromAtriplex nummularia L. (Casas et al., 1991) yielded between 3 and 5 mg of purified proteins that fully retained their antifungal activity. The entire system of overexpression, extraction, and purification could be easily scaled up for the production of several grams of protein.     

Identification of a chemoreceptor that specifically mediates chemotaxis toward metabolizable purine derivatives

Chemotaxis is an essential mechanism that enables bacteria to move toward favorable ecological niches. Escherichia coli, the historical model organism for studying chemotaxis, has five well‐studied chemoreceptors. However, many bacteria with different lifestyle have more chemoreceptors, most of unknown function. Using a high throughput screening approach, we identified a chemoreceptor from Pseudomonas putida KT2440, named McpH, which specifically recognizes purine and its derivatives, adenine, guanine, xanthine, hypoxanthine and uric acid. The latter five compounds form part of the purine degradation pathway, permitting their use as sole nitrogen sources. Isothermal titration calorimetry studies show that these six compounds bind McpH‐Ligand Binding Domain (LBD) with very similar affinity. In contrast, non‐metabolizable purine derivatives (caffeine, theophylline, theobromine), nucleotides, nucleosides or pyrimidines are unable to bind McpH‐LBD. Mutation of mcpH abolished chemotaxis toward the McpH ligands identified – a phenotype that is restored by complementation. This is the first report on bacterial chemotaxis to purine derivatives and McpH the first chemoreceptor described that responds exclusively to intermediates of a catabolic pathway, illustrating a clear link between metabolism and chemotaxis. The evolution of McpH may reflect a saprophytic lifestyle, which would have exposed the studied bacterium to high concentrations of purines produced by nucleic acid degradation.     

Correlation between hydroperoxide-induced chemiluminescence of the heart and its function

The isolated perfused rat heart emits a spontaneous ultraweak chemiluminescence. When the perfusion is stopped, light emission decreases, indicating the dependency of this phenomenon on aerobic metabolism. Emitted chemiluminescence was markedly enhanced following perfusion with 0.05 mM H₂O₂ or cumene hydroperoxide or tert-butyl hydroperoxide; substitution of O₂ for N₂ in the gassing mixture of the perfusion media significantly lowered photon emission. Lipid peroxidation, which is known to be associated with chemiluminescence, was evaluated by HPLC analysis of peroxidized and unperoxidized heart phosphatidylcholines. During hydroperoxide perfusion, coronary flow and heart rate progressively decreased, while lactic dehydrogenase was released after complete cardiac arrest. The resultant morphology of this damage corresponds to the so-called ‘stone heart’, a pattern already described in both human and experimental pathology.