Divergent directed evolution of a TetR-type repressor towards aromatic molecules.

Reprogramming cellular behaviour is one of the hallmarks of synthetic biology. To this end, prokaryotic allosteric transcription factors (aTF) have been repurposed as versatile tools for processing small molecule signals into cellular responses. Expanding the toolbox of aTFs that recognize new inducer molecules is of considerable interest in many applications. Here, we first establish a resorcinol responsive aTF-based biosensor in Escherichia coli using the TetR-family repressor RolR from Corynebacterium glutamicum. We then perform an iterative walk along the fitness landscape of RolR to identify new inducer specificities, namely catechol, methyl catechol, caffeic acid, protocatechuate, L-DOPA, and the tumour biomarker homovanillic acid. Finally, we demonstrate the versatility of these engineered aTFs by transplanting them into the model eukaryote Saccharomyces cerevisiae. This work provides a framework for efficient aTF engineering to expand ligand specificity towards novel molecules on laboratory timescales, which, more broadly, is invaluable across a wide range of applications such as protein and metabolic engineering, as well as point-of-care diagnostics.

Efficacy of 5-fluorouracil (5-FU) and low molecular weight heparin (LMWH) in high-risk pediatric retinal detachment; randomized clinical trial.

BACKGROUND: Pediatric rhegmatogenous retinal detachments (PRRDs) are complex, rare occurrences and are often related to trauma or congenital abnormalities. Children often do not recognize or report symptoms of retinal detachment. Thus at presentation, PRRD is typically advanced often with macular involvement, proliferative vitreoretinopathy (PVR), chronic duration, and poor visual acuity. Because 5-FU and LMWH are effective in different aspects in the PVR process, it was believed that a syngergistic approach to the prevention of PVR would be advantageous. METHODS: After informed consent, children under 14 years of age with high-risk PRRD underwent pars plana vitrectomy and silicone oil injection with scleral buckle divided into 2 groups in prospective randomized trial. Group A received intraoperative infusion of 5-FU (200 µg/ml) and LMWH (5 IU/ml), group B received infusion of normal saline. Primary outcome was occurrence of recurrent PRRD within 12 weeks, secondary outcomes were occurrence of PVR, best corrected visual acuity (BCVA), number and timing of secondary procedures within 12 weeks. RESULTS: The study included 42 eyes of 41 patients, 21 in group A and 21 in group B, the duration of PRRD ranged from 0.5 to 7 months in group A and 0.25-5 months in group B.The rate of recurrent PRRD was higher in group B 33% compared to 19% in group A (p = 0.292). The mean timing of occurrence of recurrent PRRD was 9.5 ± 5 weeks in group A compared to 2.86 ± 2.41 weeks in group B (p = 0.042), more patients in group B ended up with more advanced PVR (p = 0.038), BCVA was hand movement (HM) only in all cases preoperatively and improved to HM-0.3 Snellen in group A compared to light perception (PL)-0.1Snellen in group B (p = 0.035), there was no difference in any of secondary procedures but with later timing in group A 9.71 ± 3.73 weeks than in group B 4.0 ± 2.83 weeks (p = 0.042). CONCLUSION: This study concluded that the use of the 5-FU and LMWH combination in high risk PRRD resulted in lower rate of postoperative PVR, later recurrence of PRRD and better final BCVA. TRIAL REGISTRATION NUMBER: Registry: clinicaltrials.gov PRS NCT06166914 date of initial release 4/12/2023. Unique Protocol ID: 9,163,209 date 21/10/2021. Retrospectively registered.

A new fluorescence probe for sofosbuvir analysis in dosage form and spiked human plasma.

A simple, rapid, and low-cost technique was developed to allow reliable analysis of the anti-hepatitis C drug sofosbuvir in bulk, tablet form, and spiked human plasma. This method depends on the ability of sofosbuvir to quench the fluorescence of the newly synthesized 2-amino-3-cyano-4,6-dimethylpyridine (reagent 3). Elemental analysis and spectral data were used to validate the structure of the synthesized reagent. The newly synthesized reagent exhibited a satisfactory level of fluorescence emission at 365 nm after excitation at 247 nm. All experimental variables that might affect the quenching process were analyzed and optimized. Linearity, range, accuracy, precision, limit of detection (LOD), and limit of quantitation (LOQ) were all validated in accordance with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. The concentration range was shown to be linear between 0.1 and 1.5 µg/mL. The technique was effectively utilized for sofosbuvir analysis in both its tablet dosage form and spiked human plasma, with mean percentage recoveries of 100.13 ± 0.35 and 94.26 ± 1.69, respectively.

The Role of Epithelial Cell Adhesion Molecule Cancer Stem Cell Marker in Evaluation of Hepatocellular Carcinoma.

Background and Objectives: Hepatocellular carcinoma (HCC) is a prevalent form of malignancy that is characterized by high mortality rates and prognosis that remain suboptimal, largely due to treatment resistance mechanisms. Recent studies have implicated cancer stem cells (CSCs), particularly those expressing epithelial cell adhesion molecule (EpCAM), in HCC progression and resistance. In the present study, we sought to assess EpCAM expression in HCC patients and its correlation with various clinicopathological parameters. Materials and Methods: Tissue samples from 42 HCC patients were subjected to immunohistochemical staining to evaluate EpCAM expression. Clinicopathological data were obtained including the size, grade and stage of tumors, vascular invasion status, alpha-fetoprotein levels, and cirrhosis status. The Chi square and Fisher's exact tests were employed to assess the association between categorical groups. Independent Student-t test or Mann-Whitney U test was used to investigate the association between continuous patient characteristics and survival. Results: Immunohistochemical analysis revealed EpCAM expression in 52.5% of HCC cases. EpCAM-positive tumors exhibited characteristics indicative of aggressive disease, including larger tumor sizes (p = 0.006), greater tumor multiplicity (p = 0.004), higher grades (p = 0.002), more advanced stages (p = 0.003), vascular invasion (p = 0.023), elevated alpha-fetoprotein levels (p = 0.013), and cirrhosis (p = 0.052). Survival analysis demonstrated that EpCAM expression was significantly associated with lower overall rates of survival and higher rates of recurrence in HCC patients. Conclusions: Our findings suggest that EpCAM expression may serve as a prognostic biomarker for HCC with a potential role in patient management. Targeting EpCAM-positive CSCs may represent a promising approach to overcome treatment resistance and improve clinical outcomes in HCC. However, further investigation into the molecular mechanisms underlying EpCAM's role in HCC progression is warranted to facilitate the development of personalized therapeutic interventions.

Lactosylated Chitosan Nanoparticles Potentiate the Anticancer Effects of Telmisartan In Vitro and in a N-Nitrosodiethylamine-Induced Mice Model of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide. Telmisartan (TLM), a BSC class II drug, has been reported to have antiproliferative activity in HCC. However, its therapeutic activity is limited by poor bioavailability and unpredictable distribution. This work aimed to enhance TLM's liver uptake for HCC management through passive and active targeting pathways utilizing chitosan nanoparticles decorated with lactose (LCH NPs) as a delivery system. In vitro cell cytotoxicity and cellular uptake studies indicated that TLM-LCH NPs significantly (p < 0.05) enhanced the antiproliferative activity and cellular uptake percentage of TLM. In vivo bioavailability and liver biodistribution studies indicated that TLM-LCH NPs significantly (p < 0.05) enhanced TLM concentrations in plasma and the liver. The relative liver uptake of TLM from TLM-LCH NPs was 2-fold higher than that of unmodified NPs and 5-fold higher than that of plain TLM suspension. In vivo studies of a N-nitrosodiethylamine-induced HCC model revealed that administration of TLM through LCH NPs improved liver histology and resulted in lower serum alpha-fetoprotein (AFP), matrix metalloproteinase 2 (MMP-2), vascular endothelial growth factor (VEGF) levels, and liver weight index compared to plain TLM and TLM-loaded unmodified NPs. These results reflected the high potentiality of LCH NPs as a liver-targeted delivery system for TLM in the treatment of HCC.

Telmisartan-Loaded Lactosylated Chitosan Nanoparticles as a Liver Specific Delivery System: Synthesis, Optimization and Targeting Efficiency.

Hepatocellular carcinoma (HCC) has a significant economic impact and a high mortality rate. Telmisartan (TLM) is a potential therapy for HCC, but it has a limited scope in drug delivery due to unpredictable distribution and poor bioavailability. The objective of this study was to prepare, design, and in vitro evaluate lactose-modified chitosan nanoparticles (LCH NPs) as a liver-targeted nanocarrier for TLM with the potential to offer a promising HCC therapy. The combination of chitosan with lactose was successfully attained using the Maillard reaction. TLM-LCH NPs were prepared, characterized, and optimized with the developed 23 full factorial design. The optimized formulation (F1) was in vitro and in vivo characterized. LCH was synthesized with an acceptable yield of 43.8 ± 0.56%, a lactosylation degree of 14.34%, and a significantly higher aqueous solubility (6.28 ± 0.21 g/L) compared to native chitosan (0.25 ± 0.03 g/L). In vitro characterization demonstrated that, F1 had a particle size of 145.46 ± 0.7 nm, an entrapment efficiency of 90.21 ± 0.28%, and a surface charge of + 27.13 ± 0.21 mV. In vitro TLM release from F1 was most consistent with the Higuchi model and demonstrated significantly higher release at pH 5.5. Moreover, a significantly higher ratio of liver to plasma concentration was observed with TLM-LCH NPs compared to plain TLM and unmodified TLM-NPs. The obtained results nominate TLM-LCH NPs as a promising carrier for enhancing liver targeting of TLM in treatment of HCC.

The Expression of Stem Cell Marker LGR5 and Its Coexpression with Β-Catenin in Sporadic Colorectal Carcinoma and Adenoma: A Comparative Immunohistochemical Study.

Background: LGR5 is one of the most important stem cell markers for colorectal cancer (CRC), as it potentiates Wnt/Β-catenin signaling. The well-characterized deregulation of Wnt/Β-catenin signaling that occurs during adenoma/carcinoma sequence in CRC renders LGR5 a hopeful therapeutic target. We assessed the immunohistochemical expression of LGR5 and Β-catenin in normal colonic and tumorous lesions with a clinicopathological correlation. Methods: Tissue blocks and clinical data of 50 selected cases were included: 8 from normal mucosa, 12 cases of adenoma, and 30 cases of CRC, where sections were cut and re-examined and the immunohistochemical technique was conducted using anti-LGR5 and anti-Β-catenin to measure the staining density. Results: There was no expression of LGR5 in normal mucosa compared to samples of adenoma and CRC samples. The association analysis showed that CRC specimens were more likely to have strong LGR5 and Β-catenin expressions than the other two groups (p = 0.048 and p < 0.001, respectively). Specimens with high-grade dysplastic adenoma were more likely to express moderate-to-strong expression of LGR5 and Β-catenin (p = 0.013 and p = 0.036, respectively). In contrast, there were no statistically significant associations between LGR5 and Β-catenin expression with grade and stage. Conclusion: These results suggest and support the possible role of LGR5 as a potential marker of cancer stem cells in sporadic colorectal carcinogenesis in addition to a prognostic value for LGR5 and Β-catenin in adenomatous lesions according to immunohistochemical expression density. A potential therapeutic role of LGR5 in CRC is suggested for future studies based on its role in pathogenesis.

Regulation of mitochondrial temperature in health and disease.

Mitochondrial temperature is produced by various metabolic processes inside the mitochondria, particularly oxidative phosphorylation. It was recently reported that mitochondria could normally operate at high temperatures that can reach 50℃. The aim of this review is to identify mitochondrial temperature differences between normal cells and cancer cells. Herein, we discussed the different types of mitochondrial thermosensors and their advantages and disadvantages. We reviewed the studies assessing the mitochondrial temperature in cancer cells and normal cells. We shed the light on the factors involved in maintaining the mitochondrial temperature of normal cells compared to cancer cells.

Loperamide potentiates doxorubicin sensitivity in triple-negative breast cancer cells by targeting MDR1 and JNK and suppressing mTOR and Bcl-2: In vitro and molecular docking study.

Multidrug resistance (MDR) is the leading cause of treatment failure in triple-negative breast cancer (TNBC) patients treated with doxorubicin (DXR). We aimed to investigate the potential of the antidiarrheal drug Loperamide (LPR) in sensitizing TNBC cells to DXR and elucidate the underlying molecular mechanisms. Therefore, we examined the effects of DXR alone or in combination with LPR on MDA-MD-231 cells viability using MTT assay, cell cycle, and apoptosis by flow cytometry, and the expression of the MDR-related genes (MDR1 and JNK1) and cell cycle/survival genes (p21, mTOR, and Bcl-2) by quantitative reverse transcription polymerase chain reaction. Results showed that adding LPR to DXR potentiated its antiproliferation effect and reduced its IC50 by twofolds compared with DXR alone. The value of the combination index of LPR/DXR was <1 indicating a synergistic effect. Combined DXR/LPR treatment also caused G1 arrest and potentiated apoptosis more than DXR-single treatment. At the molecular levels, LPR/DXR treatment downregulated the mRNA of MDR1 (1.35-folds), JNK1 (2.5-folds), mTOR (6.6-folds), Bcl-2 (9.5-folds); while upregulated p21 gene (8-folds) compared with DXR alone. Molecular docking analyses found LPR antagonizes MDR1 and JNK1 proteins, and hence supports the in vitro studies. In conclusion, the results confirmed the potential of LPR in sensitizing TNBCs to DXR by targeting MDR1 and JNK1 and suppressing Bcl-2 and mTOR genes, while upregulating the cell cycle inhibitor gene p21. Additionally, LPR could be repurposed to reduce the therapeutic doses of DXR as indicated by the dose reduction index (DRI) and subsequently decrease its side effects.

Efficacy of Preoperative Oral Midodrine in Preventing Hypotension After Spinal Anesthesia in Young Adults: A Randomized Controlled Trial.

BACKGROUND: Midodrine was effectively used for prophylaxis against hypotensive syndromes such as postural hypotension and intradialytic hypotension, and during the recovery phase of septic shock. In our study, we aimed to assess the efficacy of prophylactic administration of midodrine tablets before spinal anesthesia in reducing the occurrence of hypotension. METHODS: This randomized placebo-controlled study embraced 67 patients aged 18 to 40 years undergoing elective knee surgery under spinal anesthesia. Patients were randomized to midodrine group (given 10-mg tablets of midodrine) or placebo group (given placebo tablets), and tablets were administered 1 hour before spinal anesthesia (intrathecal injection of 12.5-mg 0.5% hyperbaric bupivacaine and 15-µg fentanyl). The primary outcome was the occurrence of hypotension, defined as a systolic blood pressure <90 mm Hg or <80% of baseline. Secondary outcomes were hemodynamic characteristics (mean arterial pressure [MAP] and heart rate [HR]) after spinal anesthesia, ephedrine dose, and occurrence of complications including bradycardia, vasovagal attacks, reactive hypertension nausea, vomiting, and shivering. RESULTS: The number of patients who became hypotensive after spinal anesthesia was 5 (14.7%) in midodrine group versus 14 (42.4%) in the placebo group; relative risk (95% confidence interval) was 0.35 (0.14-0.85) ( P = .021). The median (interquartile range) total dose of ephedrine was significantly lower in midodrine group 0 (0-10) mg than in placebo group (0 (0-15) mg; the Hodges-Lehmann median difference (95% confidence interval) was 0 (0-5) mg ( P = .015). For MAP data, the group × time interaction was significant ( P = .038), and the MAP was significantly lower in the placebo group than in the midodrine group after intrathecal injection at 2 minutes ( P = .047), 10 minutes ( P = .045), 15 minutes ( P < .001), 20 minutes ( P = .007), 30 minutes ( P =.013), 45 minutes ( P = .029), 60 minutes ( P = .029), and at the end of surgery ( P < .001). For HR data, the group × time interaction was nonsignificant ( P = .807), and the difference in means (95% confidence interval) between groups collapsing over time was -1.4 (-3.1 to 0.2) beats/min ( P = .096). There was no significant difference between the 2 groups regarding the occurrence of complications. CONCLUSIONS: Prophylactic administration of 10-mg midodrine tablets before spinal anesthesia is an effective method in the prevention of hypotension in young adult patients undergoing elective orthopedic knee surgery.

Fan-beam projection for modulation classification in optical wireless communication systems.

The focus of most research nowadays in the field of communication technology is on increasing bandwidth in wireless connectivity. Adaptive modulation can be used to enhance efficiency of communication systems. Adaptive modulation requires modulation format identification (MFI) at the receiver side to avoid the overhead required to determine the modulation type at the receiver. We present an MFI algorithm based on fan-beam projection to generate patterns from the constellation diagrams that are more discriminative. The constellation diagrams are obtained as images for eight different modulation formats (2/4/8/16 - PSK and 8/16/32/64 - QAM). Different classifiers such as AlexNet, VGG16, and VGG19 are studied and compared for the task of MFI. Evaluation of this proposed algorithm is performed by estimating the classification accuracy at different optical signal-to-noise ratios (OSNRs) ranging from 5 to 30 dB. The simulation results reveal that the proposed algorithm succeeds in identifying the wireless optical modulation format blindly with a classification accuracy up to 100% even at low OSNR values less than 8 dB compared with the related work.

Acitretin: Could it be a new therapeutic player in the field of onychomycosis?

BACKGROUND: Onychomycosis represents a therapeutic challenge. The complete cure rate with itraconazole pulse therapy remains unsatisfactory implying the need for an effective therapeutic regimen. Given the successful treatment of recurrent dermatophytosis with isotretinoin and itraconazole, we investigated the therapeutic use of acitretin in onychomycosis. AIM: To evaluate and compare the efficacy of combined itraconazole and acitretin versus monotherapy with each in onychomycosis. PATIENTS AND METHODS: The study included 135 adult patients with finger- and/or toenail onychomycosis. They were equally subdivided into 3 groups: itraconazole pulse therapy, acitretin and combined itraconazole/acitretin therapy. The drugs were administered for 3 months. Evaluation of severity was done by onychomycosis severity index score. Potassium hydroxide microscopy and culture were performed at baseline and at the end of the study. RESULTS: Mycological and complete cure of onychomycosis was observed in 51.1% and 20% of the itraconazole group, 28.9% and 28.9% of the acitretin group, and 80% and 53.3% of the combined group. There was a statistically significant difference between groups in favour of the combined itraconazole/acitretin therapy (P ≤ .05). LIMITATIONS: Small sample and short therapy duration. CONCLUSIONS: Acitretin could be a powerful therapeutic player in the field of onychomycosis, with greater efficacy when combined with itraconazole.

On the Role of Damage Evolution in Finite Element Modeling of the Cutting Process and Sensing Residual Stresses.

This study focuses on the role of the damage evolution when estimating the failure behavior of AISI 1045 steel for sensing and measuring metal cutting parameters. A total of five Lagrangian explicit models are established to investigate the effect of applying damage evolution techniques. The Johnson-Cook failure model is introduced once to fully represent damage behavior, i.e., no damage evolution is considered, and as a damage initiation criterion in the remaining approaches. A fracture energy-based model is included to model damage propagation with different evolution rates. Temperature-dependent and temperature-independent fracture energy models are also investigated. Dry orthogonal cutting and residual stresses measurements of AISI 1045 are conducted for validation. The significance of the damage evolution is investigated using honed-tool and sharp-tool models. Including the damage evolution led to a prediction of higher workpiece temperatures, plastic strains, cutting forces, and residual stresses, with no clear differences between linear and exponential evolution rates. The role of damage evolution is more evident when temperature-dependent evolution models are used.

Potential Association between Subclinical Hypothyroidism and Childhood Migraine.

Background and Objectives: Migraine is caused by genetic susceptibility that is triggered by environmental as well as biological factors, and it is also linked to many somatic comorbidities, including clinical and subclinical hypothyroidism. We aimed to estimate the potential association between subclinical hypothyroidism (ScH) and migraine in children at our tertiary hospital. Materials and Methods: Using a case−control strategy, 200 children and adolescents were assigned to two equal groups: a case group (patients with migraine) of 100 patients and a control group of 100 patients without migraine. Clinical and biochemical parameters (TSH, FT4) were compared between the groups using statistical analysis. Results: Thyroid function comparison between the groups showed higher TSH but normal FT4 among children with migraine headache compared to the control group, which means more frequent ScH cases among the migraine group relative to the control (17% vs. 2%, p < 0.001). Obesity and overweight were more frequent among patients with migraine than the control group (8 and 5% vs. 2 and 1%, respectively). The (overweight/obese) patients with migraine had about 77% ScH and 15.4% overt hypothyroidism compared to 8% ScH and no overt hypothyroidism among normal body weight migraine patients (p < 0.001). No significant difference in the prevalence of nodular goiter between patients with migraine and controls was found. Conclusions: Based on our results, subclinical hypothyroidism is significantly linked to childhood migraine. Obesity and being overweight are more frequent among patients with migraine. Therefore, it may be logical to test the thyroid function in migraineur children, especially those with high BMI. Further studies are recommended to discover the mechanism of this association in children.

Heat Shock Proteins in the "Hot" Mitochondrion: Identity and Putative Roles.

The mitochondrion is known as the "powerhouse" of eukaryotic cells since it is the main site of adenosine 5'-triphosphate (ATP) production. Using a temperature-sensitive fluorescent probe, it has recently been suggested that the stray free energy, not captured into ATP, is potentially sufficient to sustain mitochondrial temperatures higher than the cellular environment, possibly reaching up to 50 °C. By 50 °C, some DNA and mitochondrial proteins may reach their melting temperatures; how then do these biomolecules maintain their structure and function? Further, the production of reactive oxygen species (ROS) accelerates with temperature, implying higher oxidative stresses in the mitochondrion than generally appreciated. Herein, it is proposed that mitochondrial heat shock proteins (particularly Hsp70), in addition to their roles in protein transport and folding, protect mitochondrial proteins and DNA from thermal and ROS damage. Other thermoprotectant mechanisms are also discussed.

Intralesional Measles, Mumps, and Rubella Vaccine Versus Intralesional Candida Antigen in the Treatment of Common and Plantar Warts.

BACKGROUND: Intralesional immunotherapy has been effectively used in the treatment of warts; however, comparative studies between different antigens are limited. OBJECTIVE: To evaluate the efficacy and safety of intralesional measles, mumps, and rubella (MMR) vaccine compared with intralesional Candida antigen for the treatment of multiple common and plantar warts. METHODS: Sixty-eight adult patients with multiple common and plantar warts were randomly assigned into two groups, each containing 34 patients. The first group received intralesional MMR vaccine, while the second group received intralesional Candida antigen. Each treatment was injected into the largest wart at 2-week intervals until complete clearance or for a maximum of 5 sessions. RESULTS: The overall therapeutic response was higher in the Candida antigen group (73.5%) compared with the MMR group (67.7%); however, the difference was not statistically significant. Complete clearance of common warts was higher in the Candida antigen group, while that of plantar warts was higher in the MMR group. Adverse effects were transient and well tolerated in both groups. No recurrence was detected during the 6-month follow-up period. CONCLUSION: Intralesional MMR and intralesional Candida antigen showed comparable efficacy and safety in the treatment of common and plantar warts.

A Spectral-Based Approach for BCG Signal Content Classification.

This paper has two objectives: the first is to generate two binary flags to indicate useful frames permitting the measurement of cardiac and respiratory rates from Ballistocardiogram (BCG) signals-in fact, human body activities during measurements can disturb the BCG signal content, leading to difficulties in vital sign measurement; the second objective is to achieve refined BCG signal segmentation according to these activities. The proposed framework makes use of two approaches: an unsupervised classification based on the Gaussian Mixture Model (GMM) and a supervised classification based on K-Nearest Neighbors (KNN). Both of these approaches consider two spectral features, namely the Spectral Flatness Measure (SFM) and Spectral Centroid (SC), determined during the feature extraction step. Unsupervised classification is used to explore the content of the BCG signals, justifying the existence of different classes and permitting the definition of useful hyper-parameters for effective segmentation. In contrast, the considered supervised classification approach aims to determine if the BCG signal content allows the measurement of the heart rate (HR) and the respiratory rate (RR) or not. Furthermore, two levels of supervised classification are used to classify human-body activities into many realistic classes from the BCG signal (e.g., coughing, holding breath, air expiration, movement, et al.). The first one considers frame-by-frame classification, while the second one, aiming to boost the segmentation performance, transforms the frame-by-frame SFM and SC features into temporal series which track the temporal variation of the measures of the BCG signal. The proposed approach constitutes a novelty in this field and represents a powerful method to segment BCG signals according to human body activities, resulting in an accuracy of 94.6%.

Clinical evaluation of the efficacy of trichloroacetic acid 70% after microneedling vs intradermal injection of 5-fluorouracil in the treatment of nonsegmental vitiligo; A prospective comparative study.

Vitiligo is a skin disorder commonly acquired. Although different therapies are used, they are refractory to therapy in many cases. Trauma has been reported to cause hyperpigmentation by the pigment incontinence, which results in the build-up of melanophages in the upper dermis after basal cell layer destruction. To detect the effectiveness of trichloroacetic acid (TCA) 70% in the treatment of nonsegmental vitiligo after skin microneedling by dermapen or intradermal injection of 5-fluorouracil. PATIENTS AND METHODS: A prospective comparative study was enrolled with 32 patients with vitiligo who were assigned to two equal groups. Each containing 16 patients; group 1 was treated by microneedling followed by TCA 70%, group 2 was treated by intradermal 5-FU injection. This was done every 2 weeks for 2 months. RESULTS: According to the Physician's Global Assessment, there was no significant (P < .05) difference in the therapeutic response between the two studied groups. CONCLUSIONS: Both microneedling plus TCA 70% and 5-FU intradermal injection are a simple means of treating vitiligo with cosmetically accepted repigmentation of all age groups, as well as a relatively safe alternative or additive method that can be used before (or in combination with) any of the well-known and widely approved method for stable nonsegmented vitiligo treatment.

Novel lipid-polymer hybrid nanoparticles incorporated in thermosensitive in situ gel for intranasal delivery of terbutaline sulphate.

AIM: The present work aimed to improve the bioavailability of terbutaline sulphate (TS) and to prolong its nasal residence time for the treatment of asthma. METHODS: Chitosan/pectin polyelectrolyte complex nanoparticles (CS/PC) were prepared by ionic gelation method and coated with phospholipid (PL) and then incorporated into optimised thermosensitive in situ gel. RESULTS: The optimal PL-coated nanoparticle formulation (LP1) showed the smallest particle size (345.5 nm), the highest zeta potential (32.9 mV) and the greatest percent drug released after 6 h (71%). The optimum in situ gel loaded with LP1 (NG3) showed three times greater permeation through nasal mucosa than aqueous solution of TS and revealed about 94% and 92% of the effect of IV injection of drug solution on tidal volume and peak expiratory flow in histamine treated rats, respectively. CONCLUSION: The developed PL-coated CS/PC/in situ gel could be considered as a promising intranasal formulation of TS for asthma management.

In Vitro Cytotoxicity and Cellular Uptake of Tamoxifen Citrate-Loaded Polymeric Micelles.

The main intent of this treatise was to encapsulate tamoxifen citrate (TMXC) into polymeric micellar delivery system and evaluate the influence of TMXC-loaded micelles as a promising carrier on the in vitro cytotoxicity and cellular uptake of TMXC in treatment of breast cancer. Different formulae of polymeric micelles loaded with TMXC using mixtures of different Pluronic polymers were fabricated by thin-film hydration method and evaluated for morphology, drug entrapment efficiency, particle size, surface charge, in vitro liberation of TMXC, uptake by cancer cell lines, and cytotoxic effect against breast cancer cell lines such as MCF-7. The optimal TMXC-loaded micelles exhibited nano-sized particles and entrapped about 89.09 ± 4.2% of TMXC. In vitro liberation study revealed an extended TMXC escape of about 70.23 ± 5.9% over a period of 36 h. The optimized TMXC-loaded micelles formula showed enhanced cellular uptake of TMXC by 2.28 folds and showed a significant cytotoxic effect with MCF-7 breast cancer cells compared to TMXC solution. The obtained yield proposed that Pluronic micelles could be a promising potential delivery system for anticancer moieties.