Formulation and evaluation of poly (L-lactide-co-ε-caprolactone) loaded gliclazide biodegradable nanoparticles as a control release carrier

A biodegradable nanoparticle has been used frequently as drug delivery carrier due to its better encapsulation capacity, sustained/ control release property and less toxicity. Gliclazide (GLZ) is a second generation of hypoglycemic sulfonylurea and acts selectively on pancreatic ß cell to control diabetes mellitus. The objective of this study was to produce controlled release nanoparticles of Gliclazide using poly (L-lactide-co-ε-caprolactone) (PLCL). The method was optimized using design of experiments by employing a 3-factor, 3-level Design Expert (version 8.0.7.1) Statistical Design Software and was subjected to various characterization studies including Field Emission Scanning Electron Microscopy (FE-SEM), X-ray diffraction (XRD), Encapsulation efficiency (%EE), Particle Size Distribution (PSD), etc. Formulated nanoparticles were also subjected to Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC) for studying interaction between drug and polymer and the effect of lyophilization (Freeze Drying) on developed nanoparticles.  The release profiles and encapsulation efficiencies are depended on the concentration of PLCL. These data demonstrated the efficacy of the biodegradable polymeric nanoparticles in controlling the gliclazide drug release profile as novel drug delivery system

Industrial Systems Biology of Saccharomyces cerevisiae Enables Novel Succinic Acid Cell Factory.

Saccharomyces cerevisiae is the most well characterized eukaryote, the preferred microbial cell factory for the largest industrial biotechnology product (bioethanol), and a robust commerically compatible scaffold to be exploitted for diverse chemical production. Succinic acid is a highly sought after added-value chemical for which there is no native pre-disposition for production and accmulation in S. cerevisiae. The genome-scale metabolic network reconstruction of S. cerevisiae enabled in silico gene deletion predictions using an evolutionary programming method to couple biomass and succinate production. Glycine and serine, both essential amino acids required for biomass formation, are formed from both glycolytic and TCA cycle intermediates. Succinate formation results from the isocitrate lyase catalyzed conversion of isocitrate, and from the alpha-keto-glutarate dehydrogenase catalyzed conversion of alpha-keto-glutarate. Succinate is subsequently depleted by the succinate dehydrogenase complex. The metabolic engineering strategy identified included deletion of the primary succinate consuming reaction, Sdh3p, and interruption of glycolysis derived serine by deletion of 3-phosphoglycerate dehydrogenase, Ser3p/Ser33p. Pursuing these targets, a multi-gene deletion strain was constructed, and directed evolution with selection used to identify a succinate producing mutant. Physiological characterization coupled with integrated data analysis of transcriptome data in the metabolically engineered strain were used to identify 2nd-round metabolic engineering targets. The resulting strain represents a 30-fold improvement in succinate titer, and a 43-fold improvement in succinate yield on biomass, with only a 2.8-fold decrease in the specific growth rate compared to the reference strain. Intuitive genetic targets for either over-expression or interruption of succinate producing or consuming pathways, respectively, do not lead to increased succinate. Rather, we demonstrate how systems biology tools coupled with directed evolution and selection allows non-intuitive, rapid and substantial re-direction of carbon fluxes in S. cerevisiae, and hence show proof of concept that this is a potentially attractive cell factory for over-producing different platform chemicals

A Rare Case of Situs Inversus with Mesocardia

A ten year old male child having congenital heart disease admitted with recurrent history of respiratory infection. ECHO cardioraphy showed Mesocardia, congenitally corrected TGA, bidirectional VSD and severe pulmonary valve stenosis.On sonographic evaluation showed intra-abdominal mirror imaging of all the solid organs and vessels which was suggestive of a rare presentation of Sinus inverses with Mesocardia. Corrective surgery as pulmonary valve balloon dilation or valvuloplasty and vestricular septal repair has to be done to the child for better morbidity and reducing the mortality risk. This anomaly complicates the diagnosis and management of acute abdominal conditions like appendicitis, diverticulitis and biliary coli

Comparison of glottic views and intubation times in the supine and 25 degree back-up positions

Background: We explored whether positioning patients in a 25° back-up sniffing position improved glottic views and ease of intubation. Methods: In the first part of the study, patients were intubated in the standard supine sniffing position. In the second part, the back of the operating table was raised 25° from the horizontal by flexion of the torso at the hips while maintaining the sniffing position. The best view obtained during laryngoscopy was assessed using the Cormack and Lehane classification and Percentage of Glottic Opening (POGO) score. The number of attempts at both laryngoscopy and tracheal intubation, together with the use of ancillary equipment and manoeuvres were recorded. The ease of intubation was indirectly assessed by recording the time interval between beginning of laryngoscopy and insertion of the tracheal tube. Results: Seven hundred eighty one unselected surgical patients scheduled for non-emergency surgery were included. In the back-up position, ancillary laryngeal manoeuvres, which included cricoid pressure, backwards upwards rightward pressure and external laryngeal manipulation, were required less frequently (19.6 % versus 24. 6 %, p = 0.004). The time from beginning of laryngoscopy to insertion of the tracheal tube was 14 % shorter (median time 24 versus 28 s, p = 0.031) in the back-up position. There was no significant difference in glottic views. Conclusions: The 25° back-up position improved the ease of intubation as judged by the need for fewer ancillary manoeuvres and shorter time for intubation. Trial registration: ClinicalTrials.gov Identifier: NCT02934347 registered retrospectively on 14th Oct 2016

Trichomonas vaginalis: Clinical relevance, pathogenicity and diagnosis

Trichomonas vaginalis is the etiological agent of trichomoniasis, the most prevalent non-viral sexually transmitted disease worldwide. Trichomoniasis is a widespread, global health concern and occurring at an increasing rate. Infections of the female genital tract can cause a range of symptoms, including vaginitis and cervicitis, while infections in males are generally asymptomatic. The relatively mild symptoms, and lack of evidence for any serious sequelae, have historically led to this disease being under diagnosed, and under researched. However, growing evidence that T. vaginalis infection is associated with other disease states with high morbidity in both men and women has increased the efforts to diagnose and treat patients harboring this parasite. The pathology of trichomoniasis results from damage to the host epithelia, caused by a variety of processes during infection and recent work has highlighted the complex interactions between the parasite and host, commensal microbiome and accompanying symbionts. The commercial release of a number of nucleic acid amplification tests (NAATs) has added to the available diagnostic options. Immunoassay based Point of Care testing is currently available, and a recent initial evaluation of a NAAT Point of Care system has given promising results, which would enable testing and treatment in a single visit

Cutting-edge biotechnological advancement in islet delivery using pancreatic and cellular approaches.

There are approximately 1 billion prediabetic people worldwide, and the global cost for diabetes mellitus (DM) is estimated to be $825 billion. In regard to Type 1 DM, transplanting a whole pancreas or its islets has gained the attention of researchers in the last few decades. Recent studies showed that islet transplantation (ILT) containing insulin-producing β cells is the most notable advancement cure for Type 1 DM. However, this procedure has been hindered by shortage and lack of sufficient islet donors and the need for long-term immunosuppression of any potential graft rejection. The strategy of encapsulation may avoid the rejection of stem-cell-derived allogeneic islets or xenogeneic islets. This review article describes various biotechnology features in encapsulation-of-islet-cell therapy for humans, including the use of bile acids

Metformin Prevents Nigrostriatal Dopamine Degeneration Independent of AMPK Activation in Dopamine Neurons

Metformin is a widely prescribed drug used to treat type-2 diabetes, although recent studies show it has wide ranging effects to treat other diseases. Animal and retrospective human studies indicate that Metformin treatment is neuroprotective in Parkinson’s Disease (PD), although the neuroprotective mechanism is unknown, numerous studies suggest the beneficial effects on glucose homeostasis may be through AMPK activation. In this study we tested whether or not AMPK activation in dopamine neurons was required for the neuroprotective effects of Metformin in PD. We generated transgenic mice in which AMPK activity in dopamine neurons was ablated by removing AMPK beta 1 and beta 2 subunits from dopamine transporter expressing neurons. These AMPK WT and KO mice were then chronically exposed to Metformin in the drinking water then exposed to MPTP, the mouse model of PD. Chronic Metformin treatment significantly attenuated the MPTP-induced loss of Tyrosine Hydroxylase (TH) neuronal number and volume and TH protein concentration in the nigrostriatal pathway. Additionally, Metformin treatment prevented the MPTP-induced elevation of the DOPAC:DA ratio regardless of genotype. Metformin also prevented MPTP induced gliosis in the Substantia Nigra. These neuroprotective actions were independent of genotype and occurred in both AMPK WT and AMPK KO mice. Overall, our studies suggest that Metformin’s neuroprotective effects are not due to AMPK activation in dopaminergic neurons and that more research is required to determine how metformin acts to restrict the development of PD

Is there a common water-activity limit for the three domains of life?

Archaea and Bacteria constitute a majority of life systems on Earth but have long been considered inferior to Eukarya in terms of solute tolerance. Whereas the most halophilic prokaryotes are known for an ability to multiply at saturated NaCl (water activity (a w) 0.755) some xerophilic fungi can germinate, usually at high-sugar concentrations, at values as low as 0.650-0.605 a w. Here, we present evidence that halophilic prokayotes can grow down to water activities of <0.755 for Halanaerobium lacusrosei (0.748), Halobacterium strain 004.1 (0.728), Halobacterium sp. NRC-1 and Halococcus morrhuae (0.717), Haloquadratum walsbyi (0.709), Halococcus salifodinae (0.693), Halobacterium noricense (0.687), Natrinema pallidum (0.681) and haloarchaeal strains GN-2 and GN-5 (0.635 a w). Furthermore, extrapolation of growth curves (prone to giving conservative estimates) indicated theoretical minima down to 0.611 a w for extreme, obligately halophilic Archaea and Bacteria. These were compared with minima for the most solute-tolerant Bacteria in high-sugar (or other non-saline) media (Mycobacterium spp., Tetragenococcus halophilus, Saccharibacter floricola, Staphylococcus aureus and so on) and eukaryotic microbes in saline (Wallemia spp., Basipetospora halophila, Dunaliella spp. and so on) and high-sugar substrates (for example, Xeromyces bisporus, Zygosaccharomyces rouxii, Aspergillus and Eurotium spp.). We also manipulated the balance of chaotropic and kosmotropic stressors for the extreme, xerophilic fungi Aspergillus penicilloides and X. bisporus and, via this approach, their established water-activity limits for mycelial growth (∼0.65) were reduced to 0.640. Furthermore, extrapolations indicated theoretical limits of 0.632 and 0.636 a w for A. penicilloides and X. bisporus, respectively. Collectively, these findings suggest that there is a common water-activity limit that is determined by physicochemical constraints for the three domains of life

Design of bio-nanosystems for oral delivery of functional compounds

Nanotechnology has been referred to as one of the most interesting topics in food technology due to the potentialities of its use by food industry. This calls for studying the behavior of nanosystems as carriers of biological and functional compounds aiming at their utilization for delivery, controlled release and protection of such compounds during food processing and oral ingestion. This review highlights the principles of design and production of bio-nanosystems for oral delivery and their behavior within the human gastrointestinal (GI) tract, while providing an insight into the application of reverse engineering approach to the design of those bio-nanosystems. Nanocapsules, nanohydrogels, lipid-based and multilayer nanosystems are discussed (in terms of their main ingredients, production techniques, predominant forces and properties) and some examples of possible food applications are given. Phenomena occurring in in vitro digestion models are presented, mainly using examples related to the utilization of lipid-based nanosystems and their physicochemical behavior throughout the GI tract. Furthermore, it is shown how a reverse engineering approach, through two main steps, can be used to design bio-nanosystems for food applications, and finally a last section is presented to discuss future trends and consumer perception on food nanotechnology.Miguel A. Cerqueira, Ana C. Pinheiro, Helder D. Silva, Philippe E. Ramos, Ana I. Bourbon, Oscar L. Ramos (SFRH/BPD/72753/2010, SFRH/BD/48120/2008, SFRH/BD/81288/2011, SFRH/BD/80800/2011, SFRH/BD/73178/2010 and SFRH/BPD/80766/2011, respectively) are the recipients of a fellowship from the Fundacao para a Ciencia e Tecnologia (FCT, POPH-QREN and FSE Portugal). Maria L. Flores-Lopez thanks Mexican Science and Technology Council (CONACYT, Mexico) for PhD fellowship support (CONACYT Grant number: 215499/310847). The support of EU Cost Actions FA0904 and FA1001 is gratefully acknowledged