The role of CC chemokine receptor 5 (CCR5) in islet allograft rejection

Chemokines are important regulators in the development, differentiation, and anatomic location of leukocytes. CC chemokine receptor 5 (CCR5) is expressed preferentially by CD4(+) T helper 1 (Th1) cells. We sought to determine the role of CCR5 in islet allograft rejection in a streptozotocin-induced diabetic mouse model. BALB/c islet allografts transplanted into CCR5(-/-) (C57BL/6) recipients survived significantly longer (mean survival time, 38 +/- 8 days) compared with those transplanted into wild-type control mice (10 +/- 2 days; P < 0.0001). Twenty percent of islet allografts in CCR5(-/-) animals without other treatment survived >90 days. In CCR5(-/-) mice, intragraft mRNA expression of interleukin-4 and -5 was increased, whereas that of interferon-gamma was decreased, corresponding to a Th2 pattern of T-cell activation in the target tissues compared with a Th1 pattern observed in controls. A similar Th2 response pattern was also observed in the periphery (splenocytes responding to donor cells) by enzyme-linked immunosorbent spot assay. We conclude that CCR5 plays an important role in orchestrating the Th1 immune response leading to islet allograft rejection. Targeting this chemokine receptor, therefore, may provide a clinically useful strategy to prevent islet allograft rejection.     

The Final Intraoperative Parathyroid Hormone Level: How Low Should It Go?

Background

In minimally invasive surgery for primary hyperparathyroidism (HPT), intraoperative parathyroid hormone (IOPTH) monitoring assists in obtaining demonstrably better outcomes, but optimal criteria are controversial.

Methods

The outcomes of 1,108 initial parathyroid operations for sporadic HPT using IOPTH monitoring from 1997 to 2011 were stratified by final post-resection IOPTH level. All patients had adequate follow-up to verify cure.

Results

With mean follow-up of 1.8 years (range 0.5–14.3 years), parathyroidectomy using IOPTH monitoring failed in 1.2 % of cases, with an additional 0.5 % incidence of long-term recurrence at a mean of 3.2 years (range 0.8–6.8 years) postoperatively. Operative success was equally likely with a final IOPTH drop to 41–65 pg/mL vs ≤40 pg/mL (p = 1). In the 76 patients with an elevated baseline IOPTH level that did not drop to ≤65 pg/mL, surgical failure was 43 times more likely than with a drop into normal range (13 vs. 0.3 %; p < 0.001). When the final IOPTH level dropped by >50 % but not into the normal range, surgical failure was 19 times more likely (3.8 vs. 0.2 %; p = 0.015). Long-term recurrence was more likely in patients with a final IOPTH level of 41–65 pg/mL than with a level ≤40 pg/mL (1.2 vs. 0; p = 0.016).

Conclusions

Adjunctive intraoperative PTH monitoring facilitates a high cure rate for initial surgery of sporadic primary hyperparathyroidism. A final IOPTH level that is within the normal range and drops by >50 % from baseline is a strong predictor of operative success. Patients with a final IOPTH level between 41–65 pg/mL should be followed beyond 6 months for long-term recurrence.     

Green aspects of photocatalysts during corona pandemic: a promising role for the deactivation of COVID-19 virus

The selection of a facile, eco-friendly, and effective methodology is the need of the hour for efficient curing of the COVID-19 virus in air, water, and many food products. Recently, semiconductor-based photocatalytic methodologies have provided promising, green, and sustainable approaches to battle against viral activation via the oxidative capabilities of various photocatalysts with excellent performance under moderate conditions and negligible by-products generation as well. Considering this, recent advances in photocatalysis for combating the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are inclusively highlighted. Starting from the origin to the introduction of the coronavirus, the significant potential of photocatalysis against viral prevention and -disinfection is discussed thoroughly. Various photocatalytic material-based systems including metal-oxides, metal-free and advanced 2D materials (MXenes, MOFs and COFs) are systematically examined to understand the mechanistic insights of virus-disinfection in the human body to fight against COVID-19 disease. Also, a roadmap toward sustainable solutions for ongoing COVID-19 contagion is also presented. Finally, the challenges in this field and future perspectives are comprehensively discussed involving the bottlenecks of current photocatalytic systems along with potential recommendations to deal with upcoming pandemic situations in the future.

Photocatalysts are green, eco-friendly, clean and sustainable and could be a solution to combat COVID-19 because of potential features of various types of metal oxides against viral inactivation via the generation of reactive oxidative species.     

Thiosemicarbazide functionalized carbon quantum dots as a fluorescent probe for the determination of some oxicams: application to dosage forms and biological fluids

In this study, highly fluorescent water-soluble nitrogen and sulfur doped carbon quantum dots (N, S-CQDs) were synthesized via a one-step hydrothermal process utilizing citric acid as a carbon source and thiosemicarbazide as a sulfur and nitrogen source. The obtained N, S-CQDs exhibited an intense emission band at 415 nm (λ_ex = 345 nm). In the presence of either piroxicam, tenoxicam or lornoxicam, the emission band at 415 nm was significantly quenched which might be triggered due to destruction of the surface passivation layer of the N, S-CQDs. A linear correlation was found between the reduction in the fluorescence intensity of N, S-CQDs and the concentration of each drug in the ranges of 2.0–25.0 μM, 10.0–100.0 μM and 20.0–200.0 μM with correlation coefficients of more than 0.999 for all drugs. The detection limits were 0.49 μM, 1.58 μM and 4.63 μM for piroxicam, tenoxicam and lornoxicam, respectively. The effect of experimental parameters affecting the performance of the method was investigated and optimized. The developed sensor has the advantages of simplicity, time-saving, convenience and satisfactory selectivity for determination of the studied drugs in dosage forms with high % recoveries (98.86–101.69%). The method was extended for determination of piroxicam in spiked plasma with % recoveries ranging from 97.95–101.36%. The method was validated in accordance with International Council of Harmonization (ICH) standards, and the results obtained were compared statistically to those given by reported methods, indicating no significant differences in the level of accuracy and precision. The mechanism of the quenching process was studied and elucidated. The structure–activity relationship between the three drugs and the quenching efficiency was also studied and discussed.

Highly fluorescent nitrogen and sulfur doped carbon quantum dots were synthesized via hydrothermal process using citric acid and thiosemicarbazide. The dots had an emission band at 415 nm (λ_ex = 345 nm). The polarity of the studied drugs affects the method’s sensitivity.     

Combined therapeutic hypothermia and barbiturate coma reduces interleukin-6 in the cerebrospinal fluid after aneurysmal subarachnoid hemorrhage

Inflammatory response with cytokine release is reported to correlate with clinical outcome after aneurysmal subarachnoid hemorrhage (SAH). In selected cases, hypothermia and barbiturate coma are applied as means for neuroprotection after severe SAH. Hypothermia and high-dose barbiturate are reported to attenuate the inflammatory response. In this pilot study, we assessed the effect of the combined therapy on the inflammatory response. In 15 patients with SAH, daily cerebrospinal fluid (CSF) and plasma samples were collected. Interleukin (IL)-6, tumor necrosis factor alpha (TNF-alpha), IL-1beta, systemic leukocyte, and leukocyte counts in the CSF were quantified. Group 1 represented 7 cases treated with combined therapeutic hypothermia (33 degrees C) and barbiturate coma. Group 2 represented 8 cases without combined therapy. Compared with the systemic levels, all cases showed higher cytokine levels in the CSF. Mean IL-6 level in the CSF was significantly lower in group 1 (P<0.001). The ratio between IL-6 levels in the CSF and plasma, as a parameter for intrathecal synthesis, was significantly lower in group 1 (P=0.014). Mean CSF and systemic levels of TNF-alpha of group 1 were significantly higher compared with group 2 (P=0.009 and P<0.001). The mean systemic IL-1beta level was significantly lower in group 1 (P<0.001), as well as the leukocyte counts, both, systemic and in the CSF (P<0.001 and P=0.032). The present data show a most pronounced decrease of IL-6 levels in the CSF, beside decrease in systemic IL-1beta levels, systemic leukocyte counts, and CSF leukocyte counts in group 1, which would be expected to reflect an attenuation of inflammatory response. The impact and role of TNF-alpha remains unclear.     

Primary biliary cirrhosis has high wait‐list mortality among patients listed for liver transplantation

Patients with primary sclerosing cholangitis (PSC) have frequent episodes of cholangitis with potential for high mortality while waiting for liver transplantation. However, data on wait‐list mortality specific to liver disease etiology are limited. Using United Network for Organ Sharing (UNOS) database (2002–2013), of 81 592 listed patients, 11 284 (13.8%) died while waiting for transplant. Primary biliary cirrhosis (PBC) patients (N = 3491) compared to PSC (N = 4905) differed with age (56 vs. 47 years), female gender (88% vs. 33%), black race (6% vs. 13%), and BMI (25 vs. 27), P < 0.0001 for all. A total of 993 (11.8%) patients died while waiting for the transplant list. Using competing risk analysis controlling for baseline recipient factors and accounting for receipt of liver transplantation (LT), PBC compared to patients with PSC had higher overall and 3‐month wait‐list mortality (21.6% vs. 12.7% and 5.0% vs. 2.9%, respectively, Gray's test P < 0.001), [1.25 (1.07–1.47)]. Repeat analysis including all etiologies showed higher wait‐list mortality for PBC compared to most etiologies, except for patients listed for diagnosis of alcoholic liver disease (ALD) + hepatitis C virus (HCV). Patients with PBC have high mortality while waiting for liver transplantation. These novel findings suggest that patients with PBC listed for LT may be considered for model for end‐stage disease (MELD) exception points.     

Differential expression of the human kallikrein gene 14 (KLK14) in normal and cancerous prostatic tissues

BACKGROUND: Many members of the human kallikrein gene family are differentially expressed in cancer and a few have potential as diagnostic/prognostic markers. KLK14 is a newly discovered human kallikrein gene that is mainly expressed in the central nervous system and endocrine tissues. Since KLK14 was found to be regulated by steroid hormones in prostate cancer cell lines, we hypothesized that it will be differentially expressed in prostate cancer tissues compared to their normal counterparts. METHODS: Matched prostate tissue samples from the cancerous and non-cancerous parts of the same prostates were obtained from 100 patients who underwent radical prostatectomy. Quantitative analysis of KLK14 expression levels were performed by real-time RT-PCR using SYBR Green I dye on the LightCycler trade mark system. Associations with clinico-pathological parameters were analyzed. RESULTS: KLK14 overexpression in the cancerous compared to non-cancerous tissue was found in 74% of patients (P < 0.001). Mean level of expression was 154 arbitrary units (Au) in cancerous tissues and 14.2 Au in the non-cancerous tissues. The ratio of the cancerous to non-cancerous KLK14 expression values was higher in patients with late stage (stage III) compared to stage II (P = 0.002), and in grade 3 compared to grade 1/2 tumors (P = 0.001). A statistically significant increase was also observed in patients with higher in Gleason score (>6) compared to Gleason score = 6 tumors (P = 0.027). No correlation was found between KLK14 tissue expression levels and serum prostate-specific antigen. CONCLUSIONS: KLK14 expression is significantly higher in cancerous compared to non-cancerous prostatic tissue. The up-regulation of the KLK14 gene in advanced and more aggressive tumors may indicate a possible role for the hK14 protein in tumor spread and opens the possibility of hK14 being a candidate new marker for prostate cancer diagnosis and prognosis.     

Iatrogenic iliac artery rupture and type a dissection after endovascular repair of type B aortic dissection

We report a case of two iatrogenic complications after endovascular repair of a type B aortic dissection treated for abdominal aortic branch ischemia. A rupture of the common iliac artery occurred first during the procedure. A type A dissection occurred 12 days later. The proximal part of the aortic endovascular graft had created a tear in the aortic wall resulting in a retrograde type A dissection. Although aortic endovascular grafting is apparently associated with less morbidity and mortality, potentially lethal complications, both acute and delayed, may arise.