High molecular weight cross linked chitosan nanoparticles for controlled release of 5-Fluorouracil; Enhances its bioavailability.

The aim of study was cross linking of high molecular weight chitosan nanoparticles containing 5-fluorouracil to improve dissolution rate and ultimately enhance its bioavailability by reverse emulsion/micelles method and cross-linking agent i.e. glutaraldehyde (GA 25% aqueous solution in water). The nature and outer morphologies were evaluated by scanning electron microscopy (SEM). Drug release models were functional to support way from cross linked NPs. Cross linking of 5-fluorouracil with glutaraldehyde improved dissolution rate. Mean dissolution time of 5-fluorouracil decreased significantly upon reverse emulsion/cross linking as encapsulated drug is protective and thermally stable within cross linked chitosan NPs. FTIR studies showed formation of intermolecular hydrogen bonding between 5-fluorouracil and GA-co-CHNPs. DSC studies indicated a less crystalline state of 5-fluorouracil in cross linking. SEM showed spherical nanoparticles with somewhat rough surface. 5-FU release followed Korsmeyer-Peppas model which indicate diffusion and dissociation control drug release from GA-co-CH-NPs. 5-FU cross linked chitosan nanoparticles can be safe and useful tool for other chemotherapeutic agents.

Role of Immune Status in Chemotherapy-Induced Transient Acantholytic Dermatosis.

A 79-year-old man with a recent diagnosis of acute myeloblastic leukemia received induction chemotherapy with daunorubicin and cytarabine, plus moxifloxacin and fluconazole prophylaxis. Approximately 2 weeks later, an asymptomatic eruption appeared on his trunk. He then developed a neutropenic fever and was started on aztreonam, vancomycin, voriconazole, and amikacin and was transferred to our facility from an outside hospital. Micafungin was subsequently added, and the patient defervesced within a few days.

Mucocutaneous manifestations of helminth infections: Nematodes.

In the 21st century, despite increased globalization through international travel for business, medical volunteerism, pleasure, and immigration/refugees into the United States, there is little published in the dermatology literature regarding the cutaneous manifestations of helminth infections. Approximately 17% of travelers seek medical care because of cutaneous disorders, many related to infectious etiologies. This review will focus on the cutaneous manifestations of helminth infections and is divided into 2 parts: part I focuses on nematode infections, and part II focuses on trematode and cestode infections. This review highlights the clinical manifestations, transmission, diagnosis, and treatment of helminth infections. Nematodes are roundworms that cause diseases with cutaneous manifestations, such as cutaneous larval migrans, onchocerciasis, filariasis, gnathostomiasis, loiasis, dracunculiasis, strongyloidiasis, ascariasis, streptocerciasis, dirofilariasis, and trichinosis. Tremadotes, also known as flukes, cause schistosomiasis, paragonimiasis, and fascioliasis. Cestodes (tapeworms) are flat, hermaphroditic parasites that cause diseases such as sparganosis, cysticercosis, and echinococcus.

Tocopherol succinate-loaded ethosomal gel synthesized by cold method technique: Deeper biophysical characterizations for translational application on human skin.

BACKGROUND: Tocopherols are well-known antioxidant and moisturizing agent. Tocopherol succinate (TS) are widely used in many skin products especially used in anti-aging and skin whitening product formulation. AIM: We previously reported the successful synthesis and preliminary characterizations of stable TS ethosomal gels (TSEG) (DOI: 10.1111/jocd.14907). Herein, we develop and further characterize TSEG to enhance the stability of the developed formulation with increased permeation through skin. METHODS: Cold method technique was used to prepare TS ethosomes. The developed ethosomal vesicle size was 250 nm, which allowed TS to penetrate through the stratum corneum layer and act on melanocytes. For stability study was assessed by thermogravimetric analysis (TGA) by placing TSEG and unloaded/control ethosomal gel (CEG) at various temperature conditions, that is, 8°C, 25°C, 40°C, and 40°C ± 75% RH for 3 months. Organoleptic evaluation was done in terms of color, odor, and phase separation. Transmission electron microscopy (TEM), Fourier Transform infrared spectroscopy (FTIR), x-ray diffraction spectroscopy (XRD), zeta potential (ZP) and particle size (PS) was used for TSEG physical characterizations. In vitro dissolution and ex-vivo permeation studies (using Franz diffusion cell) were performed for both TSEG and CEG formulations. Human women (N = 34) were used to evaluate in vivo biophysical parameters including erythema, melanin, moisture content, sebum level, and skin elasticity. RESULTS: Developed formulation was highly thermostable during the 3 months. Erythema, melanin, and sebum level decreased while marked improvement (p < 0.05) in moisture content and elasticity have been observed for the developed TSEG. CONCLUSION: The developed TSEG formulation was found to be efficient, safe (no adverse effects observed), stable (at least for 3 months), and easy to use for topical application with improved skin complexation and skin integrity.

Biochemical properties and biological potential of Syzygium heyneanum with antiparkinson's activity in paraquat induced rodent model.

Syzygium heyneanum is a valuable source of flavonoids and phenols, known for their antioxidant and neuroprotective properties. This research aimed to explore the potential of Syzygium heyneanum ethanol extract (SHE) in countering Parkinson's disease. The presence of phenols and flavonoids results in SHE displaying an IC50 value of 42.13 when assessed in the DPPH scavenging assay. Rats' vital organs (lungs, heart, spleen, liver, and kidney) histopathology reveals little or almost no harmful effect. The study hypothesized that SHE possesses antioxidants that could mitigate Parkinson's symptoms by influencing α-synuclein, acetylcholinesterase (AChE), TNF-α, and IL-1ß. Both in silico and in vivo investigations were conducted. The Parkinson's rat model was established using paraquat (1 mg/kg, i.p.), with rats divided into control, disease control, standard, and SHE-treated groups (150, 300, and 600 mg/kg) for 21 days. According to the ELISA statistics, the SHE treated group had lowers levels of IL-6 and TNF-α than the disease control group, which is a sign of neuroprotection. Behavioral and biochemical assessments were performed, alongside mRNA expression analyses using RT-PCR to assess SHE's impact on α-synuclein, AChE, TNF-α, and interleukins in brain homogenates. Behavioral observations demonstrated dose-dependent improvements in rats treated with SHE (600 > 300 > 150 mg/kg). Antioxidant enzyme levels (catalase, superoxide dismutase, glutathione) were significantly restored, particularly at a high dose, with notable reduction in malondialdehyde. The high dose of SHE notably lowered acetylcholinesterase levels. qRT-PCR results indicated reduced mRNA expression of IL-1ß, α-synuclein, TNF-α, and AChE in SHE-treated groups compared to disease controls, suggesting neuroprotection. In conclusion, this study highlights Syzygium heyneanum potential to alleviate Parkinson's disease symptoms through its antioxidant and modulatory effects on relevant biomarkers.

Pityriasis rosea-like drug eruption due to nortriptyline in a patient with vulvodynia.

BACKGROUND: Nortriptyline and other tricyclic antidepressants are widely used in the treatment of depression. They are also used in chronic pain syndromes such as vulvodynia. We report a case of pityriasis rosea (PR)-like eruption in a young woman who was treated with oral nortriptyline for vulvodynia. CASE REPORT: The patient presented with photosensitivity and erythematous, well-defined, oval papules and patches, with fine collarettes of scale on the dorsal hands, upper arms, and trunk. She showed a complete resolution of her rash with discontinuation of nortriptyline, thereby supporting the diagnosis of a drug-induced reaction. COMMENT: Pityriasis rosea-like drug eruptions have been associated with numerous medications, including angiotensin-converting enzyme inhibitors, antirheumatic drugs, lithium, and, more recently, biologics such as imatinib, adalimumab, and etanercept. A literature review did not reveal an association between PR-like drug eruptions and tricyclic antidepressants such as nortriptyline. We report a case of PR-like drug reaction to nortriptyline for clinical interest.

Dermatologic conditions of adult refugees following resettlement in the United States, 2015 to 2018.

Background: There is a paucity of literature regarding dermatologic conditions in migrant and refugee populations. Methods: We conducted a cross-sectional study of all adult refugees resettling in a region of Connecticut, U.S. from 7 January 2015 to 20 November 2018. We conducted a manual chart review to determine dermatologic conditions diagnosed during and within one year of resettlement. We used multivariable logistic regression to determine demographic and clinical factors associated with having any dermatologic condition. Results: We included 545 refugees primarily from Afghanistan (40.6%), Syria (24.6%) and Iraq (10.5%), with a median (interquartile range) age of 33 (28-40) years. Of the 545 participants, 213 (39.1%) had dermatologic conditions. Fifty-four participants (25%) had more than one dermatologic condition and 114 (53.5%) were diagnosed within the first month of resettlement. The most common categories of conditions were cutaneous infections (24.9%), inflammatory conditions (11.1%), and scar or burn (10.7%). Tobacco use was associated with having a cutaneous infection (OR 2.37, 95%CI:1.09-4.95), and younger age was associated with having a scar or burn (for each year increase in age, OR 0.95, 95%CI:0.91-0.99). Conclusion: Dermatologic conditions are common among adult refugees. The majority of conditions were diagnosed in the first month following resettlement suggesting that a high number of dermatologic conditions arise or go undetected and untreated during the migration process.

Pharmacokinetic variables of medium molecular weight cross linked chitosan nanoparticles to enhance the bioavailability of 5-fluorouracil and reduce the acute oral toxicity.

To prepare glutaraldehyde-based cross-linked medium molecular weight chitosan nanoparticles encapsulated with 5-Fluorouracil (5-FU), to overcome dosing frequency as well as reducing acute oral toxicity and poor bioavailability of the drug. Medium molecular weight chitosan nanoparticles (MMWCH-NPs) were prepared by reverse micelles method based on glutaraldehyde (GA) cross-linking and optimized by the process as well as formulation variables like a various drug to polymer ratio, cross-linker volumes, varying stirring speeds (rpm), different time of rotation/stirring, respectively and their effects on the mean particles size distribution and entrapment efficiency %EE and %LC of NPs. Characterization of formulations was done by FTIR studies, TEM, PXRD, TGA, Stability, and dissolution drug release studies were performed by dialysis bag technique at both pH (1.2 & 7.4) and acute oral toxicity studies in albino rabbits. The formulated nanoparticles showed a smooth morphology with smaller particle size distribution (230-550 nm), zeta potential (-15 to -18 mV) required to achieve enhanced permeation and retention effect (EPR), entrapment efficiency (%EE 12-59%). These NPs exhibited a controlled drug release profile with 84.36% of the drug over a period of 24 h. Drug release data were fitted to different kinetic models which predominantly followed Fickian diffusion mechanism (R2 = 0.972-0.976, N = 0.326-0.256). The optimized formulation (5-FU6) was observed under DSC/TGA, TEM. PXRD curves, FTIR, which confirmed thermal stability, structural integrity, amorphous state, compatibility between drug and polymer of optimized (5-FU6) as well as reduced acute oral toxicity in albino rabbits. Cross-linked medium molecular weight chitosan nanoparticles are nontoxic, well-tolerated therefore could be the future candidate for therapeutic effects as novel drug delivery carrier for anticancer drug(s).

Evaluation of Low Molecular Weight Cross Linked Chitosan Nanoparticles, to Enhance the Bioavailability of 5-Flourouracil.

The present study aimed to formulate 5-fluorouracil loaded cross linked chitosan nanoparticles based on chemical cross-linking of low molecular weight chitosan with glutaraldehyde by reverse micelles technique as 5-FU is less hydrophobic, relatively potent, has a shorter half-life, is rapidly metabolized, less tolerated, and has low oral bioavailability; therefore, we aimed to formulate potential nanocarriers of 5-FU for efficient drug delivery to specific targeted areas of action, reduce oral toxicity, improve tolerability and therapeutic outcomes of 5-FU, in a restricted fashion to enhance the bioavailability of 5-FU. Nanoparticles were formulated by the reverse micelle method based on the chemical cross-linking of glutaraldehyde (25% aqueous solution) into a w/o emulsion in different ratios. LMWCH-NPs were characterized for post-formulation parameters by mean particle size, zeta potential, %age yield, loading/entrapment efficiency, Fourier transform infrared spectroscopy (FTIR), DSC/TGA, TEM, PXRD, drug release at pH 1.2, and pH 7.4. 5-FU loaded NPs showed a size range (198 nm-200 nm) and zeta potential (-39mV to -41mV), which ensured mechanical stability and increased retention time in blood vessels by the sustained release properties of biodegradable nanocarrier drug delivery systems. % age yield showed the range 92% to 96% while % LC ranged 2.0% to 3.4% and %EE ranged 40% to 43%. The TEM images showed spherical nanoparticles. FTIR revealed the compatibility between the drug and the cross-linked polymer. DSC/TGA ensured the thermal stability of the drug, while the solid-state stability of the drug-loaded cross-linked chitosan nanoparticles was evaluated by powder X-ray diffraction (PXRD) analysis. Drug release studies were performed using the dialysis bag technique at both pH (1.2 and 7.4) to mimic the gastrointestinal tract. Highly stable NPs displayed targeted release in phosphate buffer pH 7.4 at 37°C. Fickian diffusion was the predominant release with an R2 value of 0.9975-0.9973-and an N value 0.45-0.53. Prepared nanoparticles are inert, biodegradable, and biocompatible drug delivery systems for sustained release of 5-FU with maximum therapeutic efficacy and bioavailability.

Dermatologic manifestations of COVID-19: a comprehensive systematic review.

Recent reports have suggested that there may be dermatologic manifestations of COVID-19. We searched 12 databases for peer-reviewed or pre-print published studies until July 15, 2020, for this PRISMA-compliant review (CRD42020182050). We used the Oxford Center for Evidence-Based Medicine Levels of Evidence to facilitate data synthesis. From 86 retrieved studies, we collated data on 2,560 patients with dermatologic manifestations of COVID-19. The most common findings were chilblains/pernio-like lesion (51.5%), erythematous maculopapular rashes (13.3%), and viral exanthem (7.7%). Average pediatric age was 12.9 years (SD 3.6) and adult was 34.2 years (SD 21.8). Average latency from time of upper respiratory illness symptoms to cutaneous findings was 1.5 days (SD 2.9) in children and 7.9 days (SD 10.7) in adults, ranging from -3 to 38 days. Roughly one-tenth in both populations were otherwise asymptomatic or presented with only skin findings for the entirety of the disease course; 13.3% (pediatrics) and 5.3% (adults) presented with skin issues first. Dermatologic findings may play an important role in identifying cases early and serve as an important proxy to manage spread. Further prospective data collection with international prospective registries is needed.

Bullous pemphigoid in late childhood successfully treated with mycophenolate mofetil as an adjuvant therapy.

Bullous pemphigoid is an acquired subepidermal vesiculobullous disease most commonly seen in the elderly. We report a 16-year-old girl with bullous pemphigoid who achieved disease remission with mycophenolate mofetil as an adjuvant therapy.

A Deep Learning Convolutional Neural Network Can Recognize Common Patterns of Injury in Gastric Pathology.

CONTEXT.­: Most deep learning (DL) studies have focused on neoplastic pathology, with the realm of inflammatory pathology remaining largely untouched. OBJECTIVE.­: To investigate the use of DL for nonneoplastic gastric biopsies. DESIGN.­: Gold standard diagnoses were blindly established by 2 gastrointestinal pathologists. For phase 1, 300 classic cases (100 normal, 100 Helicobacter pylori, 100 reactive gastropathy) that best displayed the desired pathology were scanned and annotated for DL analysis. A total of 70% of the cases for each group were selected for the training set, and 30% were included in the test set. The software assigned colored labels to the test biopsies, which corresponded to the area of the tissue assigned a diagnosis by the DL algorithm, termed area distribution (AD). For Phase 2, an additional 106 consecutive nonclassical gastric biopsies from our archives were tested in the same fashion. RESULTS.­: For Phase 1, receiver operating curves showed near perfect agreement with the gold standard diagnoses at an AD percentage cutoff of 50% for normal (area under the curve [AUC] = 99.7%) and H pylori (AUC = 100%), and 40% for reactive gastropathy (AUC = 99.9%). Sensitivity/specificity pairings were as follows: normal (96.7%, 86.7%), H pylori (100%, 98.3%), and reactive gastropathy (96.7%, 96.7%). For phase 2, receiver operating curves were slightly less discriminatory, with optimal AD cutoffs reduced to 40% across diagnostic groups. The AUCs were 91.9% for normal, 100% for H pylori, and 94.0% for reactive gastropathy. Sensitivity/specificity parings were as follows: normal (73.7%, 79.6%), H pylori (95.7%, 100%), reactive gastropathy (100%, 62.5%). CONCLUSIONS.­: A convolutional neural network can serve as an effective screening tool/diagnostic aid for H pylori gastritis.

Tropical dermatology: Tropical diseases caused by protozoa.

UNLABELLED: Protozoan infections are very common among tropical countries and have an important impact on public health. Leishmaniasis is the most widely disseminated protozoan infection in the world, while the trypanosomiases are widespread in both Africa and South America. Amebiasis, a less common protozoal infection, is a cause of significant morbidity in some regions. Toxoplasmosis and pneumocystosis (formerly thought to be caused by a protozoan) are worldwide parasitic infections with a very high incidence in immunocompromised patients but are not restricted to them. In the past, most protozoan infections were restricted to specific geographic areas and natural reservoirs. There are cases in which people from other regions may have come in contact with these pathogens. A common situation involves an accidental contamination of a traveler, tourist, soldier, or worker that has contact with a reservoir that contains the infection. Protozoan infections can be transmitted by arthropods, such as sandflies in the case of leishmaniasis or bugs in the case of trypanosomiases. Vertebrates also serve as vectors as in the case of toxoplasmosis and its transmission by domestic cats. The recognition of the clinical symptoms and the dermatologic findings of these diseases, and a knowledge of the geographic distribution of the pathogen, can be critical in making the diagnosis of a protozoan infection. LEARNING OBJECTIVES: After completing this learning activity, participants should be able to recognize the significance of protozoan infections worldwide, identify the dermatologic manifestations of protozoan infections, and select the best treatment for the patient with a protozoan infection.

Imported tropical diseases.

Imported tropical diseases are among the top three leading causes for morbidity and may affect up to 8% of returning travelers. Because the spectrum of dermatological manifestations seen in travelers is broad, it can be challenging for physicians to recognize and treat such conditions in a timely and efficient manner. Therefore, the present review highlights common imported tropical diseases with a focus on treatment regimens. Specifically, cutaneous larva migrans, myiasis, swimmer's itch, mycetoma, Chagas disease, and leishmaniasis are discussed. As awareness increases among travelers, immigrants, and health care providers regarding imported tropical diseases, early intervention and proper diagnosis can ensue, thus reducing morbidity and mortality in affected individuals.

Health needs of refugees: port of arrival versus permanent camp settings.

BACKGROUND: The world's refugee population has surpassed 21 million, the large majority of which resides in developing countries. Refugees have relatively high rates of healthcare utilization for management of both long-term needs, such as diabetes, and acute conditions, such as scabies. AIMS: Using interviews of stakeholders in disparate healthcare settings, we aim to elucidate both common themes and areas of difference that should be recognized and addressed as the refugee crisis continues. METHODS: This qualitative interview study compares and contrasts two settings for healthcare provision for refugees: the permanent setting of Za'atari, a camp in Jordan, versus the transitory arrival location of Lampedusa, Italy. RESULTS: We present data from 12 semi-structured interviews with experts in refugee healthcare that have experience in these two locations. We focus on issues of disease burden and health screening, organizational structures and services, cultural competency, and international response. CONCLUSIONS: We compiled recommendations to improve healthcare for refugees include recognizing differing health needs of refugees in Za'atari and Lampedusa, training providers in culturally-competent care, screening for and treating psychiatric disorders, and prioritizing agency coordination, documentation, and advocacy.

Cutaneous drug eruptions induced by sorafenib: a case series.

Sorafenib, an epidermal growth factor receptor inhibitor, is a novel treatment used for malignancies resistant to traditional chemotherapy. Epidermal growth factor receptors (EGFR) are a family of 4 transmembrane tyrosine kinase receptors that, via signal transduction pathways, mediate cell growth, differentiation, and survival. Sorafenib is a targeted drug specifically engineered to inhibit Raf serine/threonine kinases, which are part of the reticular activating system (RAS) oncogene pathway. In addition, in vitro studies have shown sorafenib to be a potent multikinase inhibitor, targeting receptor tyrosine kinases associated with tumor angiogenesis (VEGFR-2, VEGFR-3, and PDGFR-beta) and progression. Initially, approved for use in advanced renal cell carcinoma, sorafenib is being studied for the treatment of other solid tumors at our institution. During the clinical trial, 4 patients were referred to the dermatology clinic for evaluation and treatment of diffuse erythematous eruptions all occurring 8 to 10 days after initiating sorafenib at a dose of 400 mg twice daily. These eruptions occurred in demographically similar patients and displayed similar clinical characteristics and histopathological findings. Clinically, 3 of 4 patients had facial erythema, 3 of 4 had generalized macular erythema, 3 of 4 had widespread follicular-based papular eruption, and 4 of 4 had palmoplantar erythrodysesthesia. Half of the patients had cutaneous eruptions without systemic effects, while the other half had hypersensitivity reactions requiring withdrawal from clinical trial. This is the first case series illustrating drug eruptions induced by sorafenib.

Lichen planus arising in radiation therapy treatment sites.

A 59-year-old woman with a history of metastatic breast cancer presented for evaluation of hyperpigmented, reticulated, pruritic plaques on her left arm and left thigh after undergoing localized radiation therapy to the left breast and left thigh. These painful plaques with surrounding erythema appeared to follow Blaschko lines and punch biopsy results were histologically consistent with lichen planus. Herein we report a case of radiation-induced lichen planus.

Life-threatening blood loss from scratching provoked by pruritus in the bulky perineal nevocytoma variant of giant congenital melanocytic nevus in a child.

We describe a 3-year-old girl with intractable, debilitating pruritus associated with a giant congenital melanocytic nevus, resulting in life-threatening anemia from extensive bleeding skin excoriations. Multiple conventional oral and topical antipruritic medications failed to provide relief, but the patient was successfully treated with the selective serotonin 5-hydroxytryptamine type 3 inhibitor ondansetron, suggesting a serotonin-related mechanism to her pruritus.