Stimulation of hair regrowth in an animal model of androgenic alopecia using 2-deoxy-D-ribose.

Androgenic alopecia (AGA) affects both men and women worldwide. New blood vessel formation can restore blood supply and stimulate the hair regrowth cycle. Recently, our group reported that 2-deoxy-D-ribose (2dDR) is 80%-90% as effective as VEGF in the stimulation of neovascularization in in vitro models and in a chick bioassay. In this study, we aimed to assess the effect of 2dDR on hair growth. We prepared an alginate gel containing 2dDR, polypropylene glycol, and phenoxyethanol. AGA was developed in C57BL6 mice by intraperitoneally injecting testosterone (TE). A dihydrotestosterone (DHT)-treated group was used as a negative control, a minoxidil group was used as a positive control, and we included groups treated with 2dDR gel and a combination of 2dDR and minoxidil. Each treatment was applied for 20 days. Both groups treated with 2dDR gel and minoxidil stimulated the morphogenesis of hair follicles. H&E-stained skin sections of C57BL/6 mice demonstrated an increase in length, diameter, hair follicle density, anagen/telogen ratio, diameter of hair follicles, area of the hair bulb covered in melanin, and an increase in the number of blood vessels. Masson's trichrome staining showed an increase in the area of the hair bulb covered in melanin. The effects of the FDA-approved drug (minoxidil) on hair growth were similar to those of 2dDR (80%-90%). No significant benefit were observed by applying a combination of minoxidil with 2dDR. We conclude that 2dDR gel has potential for the treatment of androgenic alopecia and possibly other alopecia conditions where stimulation of hair regrowth is desirable, such as after chemotherapy. The mechanism of activity of 2dDR remains to be established.

Potential drug-drug interactions in patients presenting with osteoarthritis to community orthopaedic clinics of Abbottabad, Khyber Pakhtunkhwa: A cross-sectional study.

OBJECTIVES: Osteoarthritis (OA) causes long-term pain and disorders of lower extremities. Paracetamol is the drug of choice; however, NSAIDs, opioids and steroids are frequently employed in the symptomatic relief of OA. The prescribing of multiple analgesics leads to potential drug-drug interactions (pDDIs). The primary objective of this study was to identify the prevalence and predictors of pDDIs in OA. MATERIALS AND METHODS: A total of three hundred and eighty-six patients, either newly diagnosed or with a history of OA, were enrolled for this cross-sectional study. Data regarding patients' demographics, clinical characteristics and prescribed medications were recorded from the prescriptions and examined for the pDDIs using Medscape multidrug interaction checker. RESULTS: Among 386, most patients were females (53.4%). The most prevalent diagnoses were knee OA (39.7%) and unspecified OA (31.3%). Paracetamol and topical NSAIDs were underprescribed whereas an oral NSAID, Diclofenac, was the most frequently used drug in OA. Total of 109 pDDIs were found in 386 prescriptions, of which 63.3% DDIs were categorised as moderate, followed by minor (34.9%) and major (1.8%). CONCLUSIONS: This study finds a prevalence of DDIs and polypharmacy among the OA patients. Collaborative efforts among healthcare providers, pharmacists, and patients themselves are essential to optimize medication regimens and minimize the polypharmacy including the associated risks as well as DDIs.

Elucidating the chemical and structural composition of breast cancer using Raman micro-spectroscopy.

The current gold standard for breast cancer (BC) diagnosis is the histopathological assessment of biopsy samples. However, this approach limits the understanding of the disease in terms of biochemical changes. Raman spectroscopy has demonstrated its potential to provide diagnostic information and facilitate the prediction of the biochemical progression for different diseases in a rapid non-destructive manner. Raman micro-spectroscopy was used to characterize and differentiate breast cancer and normal breast samples. In this study, tissue microarrays of breast cancer biopsy samples (n=499) and normal breast (n=79) were analyzed using Raman micro-spectroscopy, and principal component analysis (PCA) was used for feature extraction. Linear discriminant analysis (LDA) was used for feature validation. Normal breast and breast cancer were successfully differentiated with a sensitivity of 90 % and specificity of 78 %. Dominance of lipids, specifically fatty acids, was identified in the normal tissue whereas proteins dominated the malignant spectra. Higher intensities of carotenoids, ß-carotenoids, and cholesterol were identified in the normal breast while ceramide related peaks were mostly visible in the BC spectra. The biochemical characterization achieved with Raman micro-spectroscopy showed that this technique is a powerful and reliable tool for the monitoring and diagnosis of BC, regardless of the cohort heterogeneity. Raman spectroscopy also provided a powerful insight into the biochemical changes associated with the BC progression and evolution.

Thyroxine-loaded chitosan/carboxymethyl cellulose/hydroxyapatite hydrogels enhance angiogenesis in in-ovo experiments.

Angiogenesis is one of the most important processes in repair and regeneration of many tissues and organs. Blood vessel formation also play a major role in repair of dental tissue(s) after ailments like periodontitis. Here we report the preparation of chitosan/carboxymethyl cellulose/hydroxyapatite based hydrogels, loaded with variable concentrations of thyroxin i.e., 0.1 µg/ml, 0.5 µg/ml and 1 µg/ml. Scanning electron microcopy images (SEM) showed all hydrogels were found to be porous and solution absorption study exhibited high swelling potential in aqueous media. FTIR spectra confirmed that the used materials did not change their chemical identity in synthesized hydrogels. The synthesized hydrogels demonstrated good bending, folding, rolling and stretching abilities. The hydrogels were tested in chick chorioallantoic membrane (CAM) assay to investigate their angiogenic potential. Hydrogel containing 0.1 µg/ml of thyroxine showed maximum neovascularization. For cytotoxicity analyses, preosteoblast cells (MC3T3-E1) were seeded on these hydrogels and materials were found to be non-toxic. These hydrogels with pro-angiogenic activity possess great potential to be used for periodontal regeneration.

Incidence and management of cleft lip and palate in Pakistan.

OBJECTIVE: To compare the occurrence, distribution and management of clefts of lip and palate in local patients with the available data from India and China. METHODS: The retrospective study was conducted at the Interdisciplinary Research Centre in Biomedical Materials, COMSATS University Islamabad, Lahore Campus, Lahore, Pakistan, and comprised data related to a three-month period from January to March 2015 at two medical centres in Lahore. Data from Pakistani centres was analysed based on province, gender, age and clefts of lip and palate conditions and Spearman's correlation matrix. RESULTS: Of the 1574 cases, 1061(67.4%) were from Punjab, 361(23%) Khyber Pakhtunkhwa, 85(5%) Sindh and 67(4.2%) were from Azad Jammu and Kashmir. The incidence of clefts of lip and palate was higher in males than females. There was higher awareness of the need for timely management in new borns with clefts of lip and palate. Some patients seeking secondary treatment were also being surgically corrected. There is no national registry of children born with cleft defect, making it difficult to assess the full scale of the problem.. CONCLUSIONS: Based on available data, it is likely that there are many adults who have not been treated when younger..

Fabrication, in vitro and in vivo studies of bilayer composite membrane for periodontal guided tissue regeneration.

Development of a guided occlusive biodegradable membrane with controlled morphology in order to restrict the ingrowth of epithelial cells is still a challenge in dental tissue engineering. A bilayer membrane with a non-porous upper layer (polyurethane) and porous lower layer (polycaprolactone and bioactive glass composite) with thermoelastic properties to sustain surgery treatment was developed by lyophilization. Morphology, porosity, and layers attachment were controlled by using the multi-solvent system. In vitro and in vivo biocompatibility, cell attachment, and cell proliferation were analyzed by immunohistochemistry and histology. The cell proliferation rate and cell attachment results showed good biocompatibility of both surfaces, though cell metabolic activity was better on the polycaprolactone-bioactive glass surface. Furthermore, the cells were viable, adhered, and proliferated well on the lower porous bioactive surface, while non-porous polyurethane surface demonstrated low cell attachment, which was deliberately designed and a pre-requisite for guided tissue regeneration/guided bone regeneration membranes. In addition, in vivo studies performed in a rat model for six weeks revealed good compatibility of membranes. Histological analysis (staining with hematoxylin and eosin) indicated no signs of inflammation or accumulation of host immune cells. These results suggested that the fabricated biocompatible bilayer membrane has the potential for use in periodontal tissue regeneration.

Identification of anti-cancer potential of doxazocin: Loading into chitosan based biodegradable hydrogels for on-site delivery to treat cervical cancer.

In this study, an effective, biocompatible and biodegradable co-polymer comprising of chitosan (CS) and polyvinyl alcohol (PVA) hydrogels, chemically crosslinked and impregnated with doxazocin, is reported. The chemical structural properties of the hydrogels were evaluated by Fourier Transform Infrared spectroscopy (FTIR) and physical properties were analysed by scanning electron microscopy (SEM). The swelling behaviour is an important parameter for drug release mechanism and was investigated to find out the solution absorption capacity of the synthesized hydrogels. MTT assay revealed that doxazocin loaded hydrogels significantly hindered the cell viability. Flow cytometry analysis was performed to analyse the effect of 8CLH and 4CLH on regulation of cell cycle. Moreover, in vivo anti-cancer potential of synthesized hydrogels was assessed by CAM Assay. Results displayed that 8CLH with 1mg/ml of doxazocin had prominently decreased the angiogenesis and significantly increased the number of cells in G1 phase of cell cycle. These results declared that 8CLH will be a good addition among hydrogels used for treatment of cancer by onsite delivery of drug.

Raman spectroscopy detects melanoma and the tissue surrounding melanoma using tissue-engineered melanoma models.

Invasion of melanoma cells from the primary tumor involves interaction with adjacent tissues and extracellular matrix. The extent of this interaction is not fully understood. In this study Raman spectroscopy was applied to cryo-sections of established 3D models of melanoma in human skin. Principal component analysis was used to investigate differences between the tumor and normal tissue and between the peri-tumor area and the normal skin. Two human melanoma cells lines A375SM and C8161 were investigated and compared in 3D melanoma models. Changes were found in protein conformations and tryptophan configurations across the entire melanoma samples, in tyrosine orientation and in more fluid lipid packing only in tumor dense areas, and in increased glycogen content in the peri-tumor areas of melanoma. Raman spectroscopy revealed changes around the perimeter of a melanoma tumor as well as detecting differences between the tumor and the normal tissue.

Freeze gelated porous membranes for periodontal tissue regeneration.

Guided tissue regeneration (GTR) membranes have been used for the management of destructive forms of periodontal disease as a means of aiding regeneration of lost supporting tissues, including the alveolar bone, cementum, gingiva and periodontal ligaments (PDL). Currently available GTR membranes are either non-biodegradable, requiring a second surgery for removal, or biodegradable. The mechanical and biofunctional limitations of currently available membranes result in a limited and unpredictable treatment outcome in terms of periodontal tissue regeneration. In this study, porous membranes of chitosan (CH) were fabricated with or without hydroxyapatite (HA) using the simple technique of freeze gelation (FG) via two different solvents systems, acetic acid (ACa) or ascorbic acid (ASa). The aim was to prepare porous membranes to be used for GTR to improve periodontal regeneration. FG membranes were characterized for ultra-structural morphology, physiochemical properties, water uptake, degradation, mechanical properties, and biocompatibility with mature and progenitor osteogenic cells. Fourier transform infrared (FTIR) spectroscopy confirmed the presence of hydroxyapatite and its interaction with chitosan. µCT analysis showed membranes had 85-77% porosity. Mechanical properties and degradation rate were affected by solvent type and the presence of hydroxyapatite. Culture of human osteosarcoma cells (MG63) and human embryonic stem cell-derived mesenchymal progenitors (hES-MPs) showed that all membranes supported cell proliferation and long term matrix deposition was supported by HA incorporated membranes. These CH and HA composite membranes show their potential use for GTR applications in periodontal lesions and in addition FG membranes could be further tuned to achieve characteristics desirable of a GTR membrane for periodontal regeneration.

An Auxetic structure configured as oesophageal stent with potential to be used for palliative treatment of oesophageal cancer; development and in vitro mechanical analysis.

Oesophageal cancer is the ninth leading cause of malignant cancer death and its prognosis remains poor. Dysphagia which is an inability to swallow is a presenting symptom of oesophageal cancer and is indicative of incurability. The goal of this study was to design and manufacture an Auxetic structure film and to configure this film as an Auxetic stent for the palliative treatment of oesophageal cancer, and for the prevention of dysphagia. Polypropylene was used as a material for its flexibility and non-toxicity. The Auxetic (rotating-square geometry) structure was made by laser cutting the polypropylene film. This flat structure was welded together to form a tubular form (stent), by an adjustable temperature control soldering iron station: following this, an annealing process was also carried out to ease any material stresses. Poisson's ratio was estimated and elastic and plastic deformation of the Auxetic structure was evaluated. The elastic and plastic deformation behaviours of the Auxetic polypropylene film were evaluated by applying repetitive uniaxial tensile loads. Observation of the structure showed that it was initially elastically deformed, thereafter plastic deformation occurred. This research discusses a novel way of fabricating an Auxetic structure (rotating-squares connected together through hinges) on Polypropylene films, by estimating the Poisson's ratio and evaluating the plastic deformation relevant to the expansion behaviour of an Auxetic stent within the oesophageal lumen.