Characteristics,evolution, and outcome of patients with non-infectious uveitis referred for rheumatologic assessment and management: an Egyptian multicenter retrospective study

Clinical Rheumatology - To investigate the characteristics, evolution, and visual outcome of non-infectious uveitis. Records of 201 patients with non-infectious uveitis (136 (67.7%) males and 84...     

Preparation and optimization of aloe ferox gel loaded with Finasteride-Oregano oil nanocubosomes for treatment of alopecia

Alopecia areata is a skin disorder characterized by scarless, localized hair loss that is usually managed by topical treatments that might further worsen the condition. Therefore, the current study aimed to develop nano-cubosomes loaded with finasteride (FI) and oregano oil (Or) to improve drug solubility and permeation through skin and then incorporate it into an aloe ferox gel base. An l-optimal coordinate exchange design was adopted to optimize nano-cubosomes. Phytantriol and Alkyl Acrylate were employed as the lipid material, and surfactant respectively for cubosomes manufacture. The produced formulations were assessed for their particle size, entrapment efficiency (EE%), FI steady-state flux (Jss) and minimum inhibitory concentration (MIC) against Pro-pionibacterium acnes. Optimal FI-Or-NCu had a particle size of 135 nm, EE% equals 70%, Jss of 1.85 μg/cm2.h, and MIC of 0.44 μg/ml. The optimum formulation loaded gel gained the highest drug release percent and ex vivo skin permeation compared to FI aqueous suspension, and pure FI loaded gel. Aloe ferox and oregano oil in the optimized gel formulation had a synergistic activity on the FI permeation across the skin and against the growth of p. acne bacteria which could favor their use in treating alopecia. Thus, this investigation affirms the ability of FI-Or-NCu loaded aloe ferox gel could be an effective strategy that would enhance FI release and permeation through skin and maximize its favorable effects in treating alopecia.     

Application of phosphoramidate ProTide technology significantly improves antiviral potency of carbocyclic adenosine derivatives

We report the application of phosphoramidate pronucleotide (ProTide) technology to the antiviral agent carbocyclic L-d4A (L-Cd4A). The phenyl methyl alaninyl parent ProTide of L-Cd4A was prepared by Grignard-mediated phosphorochloridate reaction and resulted in a compound with significantly improved anti-HIV (2600-fold) and HBV activity. We describe modifications of the aryl, ester, and amino acid regions of the ProTide and how these changes affect antiviral activity and metabolic stability. Separate and distinct SARs were noted for HIV and HBV. Additionally, ProTides were prepared from the D-nucleoside D-Cd4A and the dideoxy analogues L-CddA and D-CddA. These compounds showed more modest potency improvements over the parent drug. In conclusion, the ProTide approach is highly successful when applied to L-Cd4A with potency improvements in vitro as high as 9000-fold against HIV. With a view to preclinical candidate selection we carried out metabolic stability studies using cynomolgus monkey liver and intestinal S9 fractions.     

Evaluation of serum adiponectin levels in diabetic nephropathy

IntroductionDiabetic nephropathy is one of the major microvascular complications of diabetes mellitus. Adiponectin is an adipose tissue-derived cytokine that was identified in a human adipose tissue cDNA library. Serum adiponectin levels are found to be reduced in various pathological states including obesity, diabetes mellitus, ischaemic heart disease and arteriosclerosis obliterans and elevated in end stage renal diseases. Objective: to assess the level of plasma adiponectin as an early predictor of microvascular complications in patients with type 2 diabetes mellitus.Methods44 patients with type 2 diabetes recruited from outpatient diabetes clinic in Kasr Alainy hospital. All patients were subjected to full laboratory work-up including: Fasting blood glucose and Post prandial blood glucose, Glycated haemoglobin A1C, Serum creatinine, Serum total cholesterol, Triglycerides, Low density lipoprotein, High density lipoprotein, C-reactive protein titre, serum adiponectin and Urinary albumin/creatinine (UAC) ratio.ResultsThe present study demonstrated that serum adiponectin concentrations had significant positive correlation with UAC ratio (r = 0.534, p = 0.0001). Adiponectin levels showed significant positive correlation in patients with diabetes and hypertension with microalbumiuria (p = .001) or normoalbumiuria (p = 0.004).ConclusionSerum adiponectin level can be a good predictor of diabetic nephropathy in patients with type 2 diabetes mellitus.     

LIPG-promoted lipid storage mediates adaptation to oxidative stress in breast cancer

Endothelial lipase (LIPG) is a cell surface associated lipase that displays phospholipase A1 activity towards phosphatidylcholine present in high-density lipoproteins (HDL). LIPG was recently reported to be expressed in breast cancer and to support proliferation, tumourigenicity and metastasis. Here we show that severe oxidative stress leading to AMPK activation triggers LIPG upregulation, resulting in intracellular lipid droplet accumulation in breast cancer cells, which supports survival. Neutralizing oxidative stress abrogated LIPG upregulation and the concomitant lipid storage. In human breast cancer, high LIPG expression was observed in a limited subset of tumours and was significantly associated with shorter metastasis-free survival in node-negative, untreated patients. Moreover, expression of PLIN2 and TXNRD1 in these tumours indicated a link to lipid storage and oxidative stress. Altogether, our findings reveal a previously unrecognized role for LIPG in enabling oxidative stress-induced lipid droplet accumulation in tumour cells that protects against oxidative stress, and thus supports tumour progression.     

Development of novel bioadhesive granisetron hydrochloride spanlastic gel and insert for brain targeting and study their effects on rats

The aim of this study was to formulate granisetron hydrochloride (GH) spanlastic in mucoadhesive gels and lyophilized inserts for intranasal administration to improve GH bioavailability and brain targeting. Carpapol 934 and HPMC were incorporated in GH spanlastic in nasal gels (GHSpNGs). Gelatin and HPMC as matrix former, glycine as a collapse protecting and mannitol as an insert filler and sweeting agent were used to prepare GH spanlastic loaded in lyophilized inserts (GHSpNIs). The prepared GHSpNGs were characterized for pH measurement, drug content, rheology, and in vitro drug release. The prepared GHSpNIs were characterized for drug content, surface pH, GH release, and mucoadhesion. Biological investigations including pharmacokinetics studies and brain drug targeting efficiency dimensions were performed on rats (LC–MS/MS). The results showed thixotropic pseudoplastic gels and white insert with pH values in a physiological range, drug content (89.9–98.6%), (82.4–98.38%) for gel and insert, respectively and rapid release rate of GH. Biological studies showed that C_max and AUC_0–6?h in brain and plasma after intranasal administration of gel and insert were higher compared to IV administration of GH solution. A high brain targeting efficiency (199.3%, 230%) for gel and insert, respectively and a direct nose to brain transport (49.8%, 56.95%) for gel and insert, respectively confirmed that there is a direct nose to brain transport of GH following nasal administration of GH spanlastic loaded in nasal gel and insert. GHSpNIs can be considered as potential novel drug delivery system intended for brain targeting via the nasal rout of administration than GHSpNGs.     

Nanocubosomal based in situ gel loaded with natamycin for ocular fungal diseases: development,optimization, in-vitro,and in-vivo assessment

Natamycin (NT) is a synthetic broad-spectrum antifungal used in eye drops. However, it has low solubility and high molecular weight, limiting its permeation, and generally causes eye discomfort or irritation when administered. Therefore, the present study aimed to develop an ophthalmic in situ gel formulation with NT-loaded cubosomes to enhance ocular permeation, improve antifungal activity, and prolong the retention time within the eye. The NT-loaded cubosome (NT-Cub) formula was first optimized using an I-optimal design utilizing phytantriol, PolyMulse, and NT as the independent formulation factors and particle size, entrapment efficiency %, and inhibition zone as responses. Phytantriol was found to increase particle size and entrapment efficiency %. Higher levels of PolyMulse slightly increased the inhibition zone whereas a decrease in particle size and EE% was observed. Increasing the NT level initially increased the entrapment efficiency % and inhibition zone. The optimized NT-Cub formulation was converted into an in situ gel system using 1.5% Carbopol 934. The optimum formula showed a pH-sensitive increase in viscosity, favoring prolonged retention in the eye. The in vitro release of NT was found to be 71 ± 4% in simulated tear fluid. The optimum formulation enhanced the ex vivo permeation of NT by 3.3 times compared to a commercial formulation and 5.2 times compared to the NT suspension. The in vivo ocular irritation test proved that the optimum formulation is less irritating than a commercial formulation of NT. This further implies that the developed formulation produces less ocular irritation and can reduce the required frequency of administration.     

Medicinal plants and their uses by the people in the Region of Randa,Djibouti

Ethnopharmacological relevance

The article presents the local knowledge on medicinal plants and their relevance in managing health problems. Important ethnobotanical leads are given with priority species and disease categories, casting insight on future phytochemical and pharmacological studies.

Aim of the study

The use of traditional medicinal plants has been an integral part of the traditional healthcare systems in Djibouti. However, scientific studies on the traditional herbal healing systems of the various cultural groups have never been undertaken. This study has, therefore, aimed at assessing plant-related ethnomedicinal knowledge of the people in Randa Region; prioritising the plants with respect to common disease categories and inferring about prospects of new pharmacological products.

Materials and methods

Interview-based ethnobotanical field study was carried out to document the plant-based ethnomedicinal knowledge handed down to the present by the oral tradition of people living in 24 villages in Tadjourah District of Randa Region (north Djibouti). Informant Consensus Factors (ICF) and Fidelity Level (FL) values of the medicinal plants were calculated to check the level of informant agreement and the healing potentials of the species.

Results

A total of 91 plant species that belong to 72 genera and 40 families were documented. Most of these species (92%) were collected from non-cultivated areas. Their local names and traditional uses in medicine were also studied. The plant family Fabaceae was represented by the highest number of taxa (17 species). Strong informant agreements hinted at good healing potentials of some species as shown by high values of consensus factors for eye diseases (0.98), mouth diseases (0.93), kidney problems (0.89) and microbial infections (0.84). Dodonea angustifolia, Solanum cordatum, Grewia erythraea, Acalypha indica, Acacia etbaica, Fagonia schweinfurthii, Solanum coagulans, Senna alexandrina and Grewia tembensis scored high FL values emerging as promising priority species for future pharmacological screening against microbial infections.

Conclusion

The results of this study may inspire further ethnobotanical and ethnopharmacological research and investigations toward drug discovery in Djibouti and beyond.