There is sufficient evidence that diabetes during pregnancy is associated with a higher risk of neurodevelopmental anomalies including learning deficits, behavioral problems and motor dysfunctions in the offspring. Synaptophysin (SYP) is an integral membrane protein of synaptic vesicles and is considered as a marker for synaptogenesis and synaptic density. This study aimed to examine the effects of maternal diabetes in pregnancy on the expression and localization of SYP in the developing rat cerebellum. Wistar female rats were maintained diabetic from a week before pregnancy through parturition and male offspring was euthanized at postnatal day (P) 0, 7, and 14. The results revealed a significant down-regulation in the mRNA expression of SYP in the offspring born to diabetic animals at both P7 and P14 (P < 0.05 each). One week after birth, there was a significant reduction in the localization of SYP expression in the external granular (EGL) and in the molecular (ML) layers of neonates born to diabetic animals (P < 0.05 each). We also found a marked decrease in the expression of SYP in all of the cerebellar cortical layers of STZ-D group pups at P14 (P < 0.05 each). Moreover, our results revealed no significant changes in either expression or localization of SYP in insulin-treated group pups when compared with the controls (P ≥ 0.05 each). The present study demonstrated that maternal diabetes has adverse effects on the synaptogenesis in the offspring's cerebellum. Furthermore, the rigid maternal blood glucose control in the most cases normalized these negative impacts.
Background Melittin is one of the most studied antimicrobial peptides, and several in vitro experiments have demonstrated its antibacterial efficacy. However, there is evidence showing melittin has non-promising effects such as cytotoxicity and hemolysis. Therefore, concerns about unwanted collateral toxicity of melittin lie ahead in the path toward its clinical development. With these considerations, the present study aimed to fill the gap between in vitro and in vivo studies. Methods In the first step, in vitro toxicity profile of melittin was assessed using cytotoxicity and hemolysis tests. Next, a maximum intraperitoneal (i.p.) sub-lethal dose was determined using BALB/c mice. Besides toxicity, antimicrobial efficacy of melittin against extensively drug-resistant (XDR) Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), and KPC-producing Klebsiella pneumonia (KPC-KP) pathogens were tested using both in vitro and in vivo methods. Results Melittin showed extensive hemolysis (HD50 = 0.44 µg/mL), and cytotoxicity (IC50 = 6.45 µg/mL) activities with i.p. LD50 value of 4.98 mg/kg in BALB/c mice. In vitro antimicrobial evaluation showed melittin MIC range from 8 to 32 µg/mL for the studied pathogens. Treatment of infected mice with repeated sub-lethal doses of melittin (2.4 mg/kg) displayed no beneficial effect on their survival and peritoneal bacterial loads. Conclusions These results indicate that melittin at its safe dose could not exhibit antimicrobial activity, which hinders its application in clinical practice.
Background and Objectives In vitro studies have shown that CO2 lasers operating at the highly absorbed 9.3 and 9.6-μm wavelengths with a pulse duration in the range of 10–20-microsecond are well suited for the efficient ablation of enamel and dentin with minimal peripheral thermal damage. Even though these CO2 lasers are highly promising, they have yet to receive FDA approval. Clinical studies are necessary to determine if excessive heat deposition in the tooth may have any detrimental pulpal effects, particularly at higher ablative fluencies. The purpose of this study was to evaluate the pulpal safety of laser irradiation of tooth occlusal surfaces under the conditions required for small conservative preparations confined to enamel. Study Design/Materials and Methods Test subjects requiring removal of third molar teeth were recruited and teeth scheduled for extraction were irradiated using a pulsed CO2 laser at a wavelength of 9.3 μm operating at 25 or 50 Hz using a incident fluence of 20 J/cm2 for a total of 3,000 laser pulses (36 J) for both rates with water cooling. Two control groups were used, one with no treatment and one with a small cut made with a conventional high-speed hand-piece. No anesthetic was used for any of the procedures and tooth vitality was evaluated prior to treatment by heat, cold and electrical testing. Short term effects were observed on teeth extracted within 72 hours after treatment and long term effects were observed on teeth extracted 90 days after treatment. The pulps of the teeth were fixed with formalin immediately after extraction and subjected to histological examination. Additionally, micro-thermocouple measurements were used to estimate the potential temperature rise in the pulp chamber of extracted teeth employing the same irradiation conditions used in vivo. Results Pulpal thermocouple measurements showed the internal temperature rise in the tooth was within safe limits, 3.3±4°C without water cooling versus 1.7±6°C with water-cooling, n=25, P<0.05. None of the control or treatment groups showed any deleterious effects on pulpal tissues and none of the 29 test-subjects felt pain or discomfort after the procedure. Only two test-subjects felt discomfort from “cold sensitivity” during the procedure caused by the water-spray. Conclusion It appears that this CO2 laser can ablate enamel safely without harming the pulp under the rate of energy deposition employed in this study. Lasers Surg.
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