The protective effect of carvacrol on bevacizumab-related skin injury in rats: a biochemical and histopathological evaluation.

PURPOSE: Bevacizumab is a recombinant humanized monoclonal antibody that specifically binds to vascular endothelial growth factor (VEGF). Cutaneous side effects of bevacizumab are seen with substantial frequency and may require the interruption of the treatment. The aim of the study was to conduct a biochemical and histopathological investigation of the effects of carvacrol against the possible oxidative skin damage caused by bevacizumab in rats. MATERIALS AND METHODS: A total of 18 adult male Wistar albino rats were randomly assigned to three groups as healthy (H group; n = 6), bevacizumab alone (B group; n = 6), and carvacrol + bevacizumab (CB group; n = 6). Carvacrol was injected intraperitoneally (IP) at a dose of 50 mg/kg in the CB group. Sterile salt solution (0.9% NaCl) was used as a solvent for the H and B groups. One hour after the administration of carvacrol and solvent, bevacizumab at a dose of 10 mg/kg IP was administered to the CB and B groups. Bevacizumab was given once daily for a total of two doses, 15 days apart. Carvacrol was administered once daily for one month. After that period, all animals were sacrificed and their skin tissues removed. Malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPO), catalase (CAT), superoxide dismutase (SOD), total oxidant status (TOS), and total antioxidant status (TAS) levels in rats' skin tissues were biochemically evaluated. The parameters were measured with spectrophotometric method by using a microplate reader (BioTek, Winooski, VT, USA). The skin tissues were also examined histopathologically by the pathologist (blind) for the study groups. RESULTS: The MDA and TOS levels of the H and CB groups were significantly lower than the B group (p < 0.05). The mean scores of the other biochemical levels (GSH, GPO, CAT, SOD, TAS) in the H group were significantly higher than in the B and CB groups. Pathological examination of H group was normal. In B group epidermal atrophy, abnormal keratin accumulation, degenerated hair follicles, edoema and inflammatory cells accumulation in the dermis were observed. In the CB group, these findings were significantly improved. CONCLUSION: The positive effect of carvacrol against possible local oxidative skin damage due to bevacizumab in rats was demonstrated. In addition, more detailed studies are required to clarify the mechanism of the protective effect of carvacrol against bevacizumab-induced skin toxicity. The effect should be evaluated through further human studies, as well as studies using different doses of carvacrol.

Johanson-Blizzard's Syndrome with a Novel UBR1 Mutation.

Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive genetic disorder, characterized by exocrine pancreatic insufficiency, a distinct abnormal facial appearance and varying degrees of growth retardation. Ubiquitin protein ligase E3 component n-recognin 1 ( UBR1 ) gene mutations are responsible for the syndrome. Here, we describe a 2-month-old female infant, who presented with oily diarrhea, facial dysmorphia, scalp defect, hearing defects, and growth impairment. Molecular genetic testing revealed a novel frameshift mutation in UBR1 , c.4027_4028 del (p.Leu1343Valfs*7), which was not previously described in JBS in the literature.

A rare case of atrophic dermatofibroma with dermoscopic findings.

BACKGROUND: Dermatofibroma, also known as cutaneous benign fibrous histiocytoma, is a common skin tumour. AIM: The aim of this paper was to present a rare variant of dermatofibroma, atrophic dermatofibroma, emphasizing histopathological and dermoscopic features. PATIENTS/METHODS: A case of atrophic dermatofibroma in a female patient with the characteristic histopathological features and newly demonstrated dermoscopic findings is presented. RESULTS: A 54-year-old female presented with a depressed reddish lesion on the back showing histopathological findings of atrophic dermatofibroma. The dermoscopy of the lesion revealed a peripheral pigment network surrounding a pink-reddish colouration around a central whitish scar-like patch with white-yellow scales which was not an exact match with the description in the literature. CONCLUSION: Atrophic dermatofibroma is a rare variant that presents as an atrophic, depressed skin lesion which can easily be overlooked. Atrophic dermatofibroma should be considered in the differential diagnoses of atrophic, depressed lesions on the upper body of middle-aged women. The case of atrophic dermatofibroma presented here showed typical histopathologic findings with atypical dermoscopic features.

Serum irisin level, insulin resistance, and lipid profiles in patients with hidradenitis suppurativa: a case-control study

Abstract Background: Hidradenitis suppurativa is a chronic inflammatory skin disease of terminal follicular acroinfundibulum. Objectives: This study aimed to evaluate serum irisin, plasma glucose, insulin, and lipid levels in hidradenitis suppurativa, and elucidate possible associations with disease activity, inflammatory, or metabolic parameters. Methods: This case-control study included 37 patients (M/F: 9/28) and 37 sex-, age- and body mass index -matched healthy controls (M/F: 11/26). Demographic data, Hurley stage of disease, fasting glucose, insulin, total cholesterol, high density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, C-reactive protein levels, erythrocyte sedimentation rate, hematologic parameters, and serum irisin were assessed. Results: The hidradenitis suppurativa group had significantly higher waist circumference than controls (p < 0.001). Insulin resistance, defined as a homeostatic model assessment for insulin resistance value greater than 2.5, was observed in 45.9% of patients and 8.1% of controls (p = 0.003), whereas metabolic syndrome was observed in 32.4% of patients and 5.4% of controls (p < 0.001). Furthermore, plasma triglycerids, glucose, and insulin levels were significantly higher in the hidradenitis suppurativa (p = 0.013, p = 0.001, and p = 0.004), respectively. Mean irisin level was insignificantly higher in the hidradenitis suppurativa group (37.4 ± 32.6) than in controls (26.2 ± 24.7, p = 0.217). Study limitation: Physical activity and the exercise levels of participants were not documented. Conclusion: This study indicates that hidradenitis suppurativa patients have higher serum irisin, fasting plasma glucose, insulin, and triglycerides levels than healthy controls. Thus, the authors suggest that hidradenitis suppurativa patients should be evaluated for insulin resistance and metabolic syndrome, and monitored accordingly.

Serum irisin level, insulin resistance, and lipid profiles in patients with hidradenitis suppurativa: a case-control study.

BACKGROUND: Hidradenitis suppurativa is a chronic inflammatory skin disease of terminal follicular acroinfundibulum. OBJECTIVES: This study aimed to evaluate serum irisin, plasma glucose, insulin, and lipid levels in hidradenitis suppurativa, and elucidate possible associations with disease activity, inflammatory, or metabolic parameters. METHODS: This case-control study included 37 patients (M/F: 9/28) and 37 sex-, age- and body mass index -matched healthy controls (M/F: 11/26). Demographic data, Hurley stage of disease, fasting glucose, insulin, total cholesterol, high density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, C-reactive protein levels, erythrocyte sedimentation rate, hematologic parameters, and serum irisin were assessed. RESULTS: The hidradenitis suppurativa group had significantly higher waist circumference than controls (p<0.001). Insulin resistance, defined as a homeostatic model assessment for insulin resistance value greater than 2.5, was observed in 45.9% of patients and 8.1% of controls (p=0.003), whereas metabolic syndrome was observed in 32.4% of patients and 5.4% of controls (p<0.001). Furthermore, plasma triglycerids, glucose, and insulin levels were significantly higher in the hidradenitis suppurativa (p=0.013, p=0.001, and p=0.004), respectively. Mean irisin level was insignificantly higher in the hidradenitis suppurativa group (37.4±32.6) than in controls (26.2±24.7, p=0.217). STUDY LIMITATION: Physical activity and the exercise levels of participants were not documented. CONCLUSION: This study indicates that hidradenitis suppurativa patients have higher serum irisin, fasting plasma glucose, insulin, and triglycerides levels than healthy controls. Thus, the authors suggest that hidradenitis suppurativa patients should be evaluated for insulin resistance and metabolic syndrome, and monitored accordingly.

H syndrome with a novel homozygous SLC29A3 mutation in two sisters.

H syndrome (OMIM 602782) is a recently defined autosomal recessive genodermatosis. Cutaneous findings of H syndrome include hyperpigmentation, hypertrichosis, and induration, while hearing loss, heart anomalies, hepatomegaly, hypogonadism, hyperglycemia (diabetes mellitus), low height (short stature), hallux valgus (flexion contractures), and hematological abnormalities are the extracutaneous abnormalities. We report a novel homozygous missense mutation, c.416T > C p.(Leu139Pro), in the SLC29A3 (NM_001174098.1) gene in two sisters with H syndrome presenting with different phenotypes.

[Dermatomyositis presenting with low back pain]. / Bel agrisi ile basvuran dermatomiyozit olgusu.

Dermatomyositis (DM) is a rare connective tissue disease characterized by skin lesions and inflammatory changes observed in muscle biopsy findings. A definitive diagnosis of DM requires a characteristic rash in addition to proximal muscle weakness and muscle enzyme level elevation. DM is twice as common in women as men, with an age of onset of approximately 50 years. This case report describes a 29-year-old patient with low back pain and proximal muscle weakness in the legs diagnosed as lumbar disc herniation who was then referred by the neurosurgery department to our clinic. A physical examination revealed the characteristic skin lesions for dermatomyositis. Needle electromyography and a skin biopsy were performed, and corticosteroid treatment was initiated. In misdiagnosed patients, fatty infiltration in the muscles may cause irreversible weakness and gait disturbance. Early suppression of inflammation is important and can yield a dramatic response to treatment.

Evaluation of monocyte to high-density lipoprotein ratio, lymphocytes, monocytes, and platelets in psoriasis,

Abstract Background: Psoriasis is a chronic immune-mediated inflammatory skin disease that is associated with cardiovascular comorbidities. Objectives: The objective of this retrospective study is to assess the C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio as inflammatory markers in patients with psoriasis and to search for a relationship between these parameters and psoriasis severity, as defined by the psoriasis area and severity index. Methods: There were 94 patients with psoriasis and 118 healthy controls enrolled in the study. The C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio values of two groups were retrospectively evaluated. Results: Statistically significant differences were observed in terms of C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio between the patient and control groups (p = 0.001, p = 0.003, p = 0.038, and p = 0.007, respectively). Positive correlations were found between the psoriasis area and severity index and the values of C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio (r: 0.381; p < 0.01, r: 0.203; p < 0.05, r: 0.268; p < 0.01, r: 0.374; p < 0.01, r: 0.294; p < 0.01, respectively). Study limitations: The small sample size and the retrospective design of the study are limitations. Conclusion: Elevated C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio were significantly associated with psoriasis. A positive correlation between C-reactive protein and monocyte-to-high-density-lipoprotein ratio leads to the suggestion that monocyte-to-high-density-lipoprotein ratio might be a reliable parameter in psoriasis during the follow-up. The relationship between the diasease and inflammatory parameters might provide early detection of cardiovascular morbidities in psoriasis patients.

Evaluation of monocyte to high-density lipoprotein ratio, lymphocytes, monocytes, and platelets in psoriasis.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease that is associated with cardiovascular comorbidities. OBJECTIVES: The objective of this retrospective study is to assess the C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio as inflammatory markers in patients with psoriasis and to search for a relationship between these parameters and psoriasis severity, as defined by the psoriasis area and severity index. METHODS: There were 94 patients with psoriasis and 118 healthy controls enrolled in the study. The C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio values of two groups were retrospectively evaluated. RESULTS: Statistically significant differences were observed in terms of C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio between the patient and control groups (p=0.001, p=0.003, p=0.038, and p=0.007, respectively). Positive correlations were found between the psoriasis area and severity index and the values of C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio (r: 0.381; p<0.01, r: 0.203; p<0.05, r: 0.268; p<0.01, r: 0.374; p<0.01, r: 0.294; p<0.01, respectively). STUDY LIMITATIONS: The small sample size and the retrospective design of the study are limitations. CONCLUSION: Elevated C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio were significantly associated with psoriasis. A positive correlation between C-reactive protein and monocyte-to-high-density-lipoprotein ratio leads to the suggestion that monocyte-to-high-density-lipoprotein ratio might be a reliable parameter in psoriasis during the follow-up. The relationship between the diasease and inflammatory parameters might provide early detection of cardiovascular morbidities in psoriasis patients.

The Effects of Systemic Psoriasis Therapies on the C-Reactive Protein and the Neutrophil-Lymphocyte Ratio.

BACKGROUND: Currently, no generally accepted laboratory marker for monitorizing the disease activity and therapy response of psoriasis is known. OBJECTIVE: The aim of the study is to evaluate the effects of systemic therapies on C-reactive protein (CRP) and the neutrophil-lymphocyte ratio (NLR) in psoriasis. METHODS: One hundred patients with psoriasis treated with narrow band ultraviolet B, acitretin, cyclosporine, methotrexate, adalimumab, etanercept, and ustekinumab were prospectively evaluated. At baseline and at week 12, CRP, NLR, and Psoriasis Area and Severity Index (PASI) were evaluated. RESULTS: A statistically significant decrease was observed in PASI scores, CRP, and NLR values from the baseline to the 12-week visit (p=0.001, p=0.001, p=0.001, respectively). The reduction in PASI scores and NLR values was positively correlated (r=0.460, p=0.001). The comparisons between treatment groups revealed that the median decrease in NLR values was statistically higher in the adalimumab group than in the methotrexate group (p=0.007). And the median decrease in PASI scores was significantly higher in the adalimumab group compared with the methotrexate and acitretin therapy group (p=0.007, p=0.042, respectively). CONCLUSION: In the present study, systemic therapy of psoriasis was demonstrated to decrease the levels of CRP and NLR, which are known to be indicators of systemic inflammation and cardiovascular comorbidities.

Plasma Ischemia-Modified Albumin Levels and Dynamic Thiol/Disulfide Balance in Sickle Cell Disease: A Case-Control Study

Objective: Sickle cell disease (SCD), described as a group of inherited blood disorders, affects millions of people throughout the world and is particularly common in the southern part of Turkey. We aimed to determine the relationship between ischemia-modified albumin (IMA) and the dynamic thiol/disulfide balance in SCD. Materials and Methods: Fifty-four adult SCD patients and 30 healthy controls were included in the study. The 54 adult patients included 30 (56%) males and 24 (44%) females with a mean age of 28.3±8.4 years (minimum-maximum: 18-46 years). Of the 54 patients, 46 had homozygous sickle cell anemia (HbSS) and 8 had sickle/ß-thalassemia (HbS/ß+-thalassemia). Fasting blood samples were collected. After centrifugation at 1500×g for 10 min, plasma samples were portioned and stored at -80 °C. IMA levels were determined by albumin cobalt binding test, a colorimetric method. Total and native thiols and disulfide were analyzed with a novel spectrophotometric method. Results: We found significantly lower levels of native thiol (-SH) (284.0±86.3 µmol/L), disulfide levels (14.6±7 µmol/L), and total thiols (-SH + -S-S-) (313.0±89.3 µmol/L) in SCD patients compared to healthy controls (respectively 417.0±54.2, 22.7±11.3, and 462.0±58.7 µmol/L). Plasma albumin levels (34.9±7.9 g/L) were lower and IMA levels (13.6±3.1 g/L) were higher in SCD patients compared to controls (respectively 43.5±3.1 and 8.4±1.6 g/L). Plasma albumin levels were strongly correlated with both plasma native (r=0.853; p=0.0001) and total thiols (r=0.866; p=0.0001). Conclusion: Decreased plasma native and total thiol levels and increased IMA levels are related to increased oxidative stress and provide an indirect and quick reflection of the oxidative damage in SCD patients.

Three-component synthesis and carbonic anhydrase inhibitory properties of novel octahydroacridines incorporating sulfaguanidine scaffold.

Novel sulfaguanidines incorporating acridine moiety were synthesized by the reaction of cyclohexane-1,3-dione, sulfaguanidine, and aromatic aldehydes. Synthesis of these compounds was performed in water at room temperature, and their structures were confirmed by using spectral analysis (IR, 1H-NMR, 13C-NMR, and HRMS). Human carbonic anhydrase isoenzymes (hCA I and II) were purified from erythrocyte cells with affinity chromatography. hCA I was purified 83.40-fold with a specific activity, 1060.9 EU mg protein-1, and hCA II was purified 262.32-fold with a specific activity, 3336.8 EU mg protein-1. The inhibitory effects of newly synthesized sulfaguanidines and acetazolamide, (AAZ) as a control compound, on hydratase and esterase activities of these isoenzymes have been studied in vitro. Synthesized compounds have moderate inhibition potentials on hCA I and hCA II isoenzymes. IC50 values of compounds for esterase activity are in the range of 118.4 ± 7.0 µM-257.5 ± 5.2 µM for hCA I and 86.7 ± 3.0 µM-249.4 ± 10.2 µM for hCA II, respectively.