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We have recently identified a pool of intracellular β1 adrenergic receptors (β1ARs) at the sarcoplasmic reticulum (SR) crucial for cardiac function. Here, we aim to characterize the integrative control of intracellular catecholamine for subcellular β1AR signaling and cardiac function. Using anchored Förster resonance energy transfer (FRET) biosensors and transgenic mice, we determined the regulation of compartmentalized β1AR-PKA signaling at the SR and plasma membrane (PM) microdomains by organic cation transporter 3 (OCT3) and monoamine oxidase A (MAO-A), two critical modulators of catecholamine uptake and homeostasis. Additionally, we examined local PKA substrate phosphorylation and excitation-contraction coupling in cardiomyocyte. Cardiac-specific deletion of MAO-A (MAO-A-CKO) elevates catecholamines and cAMP levels in the myocardium, baseline cardiac function, and adrenergic responses. Both MAO-A deletion and inhibitor (MAOi) selectively enhance the local β1AR-PKA activity at the SR but not PM, and augment phosphorylation of phospholamban, Ca2+ cycling, and myocyte contractile response. Overexpression of MAO-A suppresses the SR-β1AR-PKA activity and PKA phosphorylation. However, deletion or inhibition of OCT3 by corticosterone prevents the effects induced by MAOi and MAO-A deletion in cardiomyocytes. Deletion or inhibition of OCT3 also negates the effects of MAOi and MAO-A deficiency in cardiac function and adrenergic responses in vivo. Our data show that MAO-A and OCT3 act in concert to fine-tune the intracellular SR-β1AR-PKA signaling and cardiac fight-or-flight response. We reveal a drug contraindication between anti-inflammatory corticosterone and anti-depressant MAOi in modulating adrenergic regulation in the heart, providing novel perspectives of these drugs with cardiac implications.

Objective: Neoadjuvant chemotherapy (NACT) is widely used for treating locally advanced Breast cancer (LABC). However, development of multidrug resistance (MDR) is the main underlying factor for chemoresistance. Technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) is a substrate for MDR. This study aimed to analyze the relationship between expression of MDR-related proteins (P-gp and Bcl-2) and 99mTc-MIBI uptake and retention in BC tumor cells, pathologic response to NACT, disease free survival (DFS) and overall survival (OS)., Methods: prospective analysis recruited 31 patients with LABC who received NACT between January 2019 and March 2020. 99mTc-MIBI planar and SPECT/CT imaging was conducted before and after NACT. Qualitative and quantitative analyses were performed, pre and post-NACT early and delayed lesion to non-lesion (LNL) ratios, and retention index (RI) of 99mTc-MIBI were calculated. Expression of P-gp and Bcl-2 in tumor cells was determined by immunohistochemistry., Results: Quantitively, inter-reader ICC for SPECT/CT based quantification was consistently higher than that of planar images. Post-NACT LNL ratios were significantly higher in patients with pathologic persistent disease (PPD). A change in RI between pre- and post-NACT scans demonstrated a significant association with DFS with a hazard ratio of 0.7 (95%CI: 06-1.0). Qualitatively, SPECT/CT was significantly more accurate compared to planar imaging in identifying residual viable tumor (81% compared to 57%).  Her2neu positivity and high post-operative Bcl-2 and P-gp were associated with worse DFS. A significant association was found between increased expression of post-NACT Bcl-2 and PPD, advanced tumor stage and poor OS., Conclusion: 99mTc-MIBI SPECT/CT based qualitative evaluation of BC response to NACT is more accurate than planar imaging. Post-NACT MIBI retention is positively correlated with P-gp and Bcl-2 expression. 99mTc-MIBI SPECT/CT may predict MDR development. High post-NACT Bcl-2 expression is significantly associated with advanced tumor stage and OS. High post-NACT P-gp expression has a worse impact on pathologic response and DFS.

Background: Cell therapy is a promising method for improving healing in chronic ulcers through delivery of isolated adipose-derived stromal vascular fraction. Objectives: This study investigates the autologous stem cell yield of adipose tissue and its efficacy in chronic ulcers compared with conventional methods. Methods: This study was a randomized controlled trial. After the study design and protocol were established and ethical committee approval was obtained, we enrolled 100 patients divided into study and control groups. In the study group, we performed debridement and autologous stem cell injection every 3 weeks. The control group was treated with debridement and conventional dressing. Assessments included clinical and histological parameters. Results: The study group showed improved healing. Conclusion: Using autologous adipose-derived stromal vascular fraction cells is an effective treatment method for chronic ulcers. This study was registered on the Pan-African Clinical Trial Registry and the number of the registry was PACTR201709002519185.

Colorectal carcinoma (CRC) is one of the most lethal malignancies, it ranks third in cancer-related morbidity and mortality. Although great progress has been made in early diagnosis and combined treatment of CRC, the prognosis of patients remains poor owing to the high rate of recurrence and distant metastasis. CXCR7 belongs to chemokine receptor family and has been identified as a novel receptor for CXCL12. It plays an important role in development and in progression of cancer to metastatic stage., The Aim of Study: To evaluate the immunohistochemical expression of CXCR7 in colorectal adenoma and carcinoma and to analyze its correlation with clinicopathological factors. This is retrospective study including 58 colonic adenocarcinoma specimens and 18 cases of colonic adenoma., Results: CXCR7 showed positive cytoplasmic expression in two out 18 cases of colorectal adenoma (11%) and 42 out of 58 cases of CRC (72.4%) with a significant difference between both (p < 0.001). We found a significant correlation between upregulation of CXCR7 and presence of lymphovascular tumor emboli, presence of lymph node metastasis and advanced TNM stage of the CRC. The association of the CXCR7 with patient age, sex, tumor size, depth of invasion and tumor cell differentiation was found to be non-significant. Regarding colonic adenoma, we found no significant association between CXCR7 expression on one hand and patient age, sex, tumor size, histologic type and degree of dysplasia on the other hand., Conclusion: CXCR7 in CRC may act as a novel predictive indicator for prognosis and even be a potential molecular target for anticancer therapies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Aims: Galectins comprise a large family of calcium independent lectins. Galectin-1 and galectin-3 contribute to neoplastic transformation, angiogenesis, and tumor metastasis in some cancers. This study aimed at studying the immunohistochemical expression of both galectin-1 and galectin-3 in renal cell carcinoma (RCC) variants and detecting the possible association of galectins with various clinicopathological parameters., Materials and Methods: Sections from 67 formalin-fixed paraffin-embedded tissue blocks of RCC variants were stained with galectin-1 and galectin-3. Expression was assessed in tumor tissue and adjacent renal parenchyma and was correlated with clinicopathological criteria., Results: In apparently normal renal parenchyma adjacent to tumor tissue, galectin-1 was expressed in 27 (40.2%) of specimens in renal tubules and glomeruli, while 34 (50.7%) of specimens showed galectin-3 expression in renal tubules sparing glomeruli. In tumor tissue, galectin-1 showed high expression in 47 (70.1%) and low expression in 20 (29.9%) of specimens. Galectin-3 had high expression in 15 (22.4%) and low expression in 52 (77.6%) of specimens. Significant association was detected between expression of galectin-1 and galectin-3 and the type of RCC (P = 0.032) and (P = 0.006), respectively. Significant inverse association was detected between the expression of galectin-3 and the presence of tumor haemorrhage and necrosis (P = 0.014) and (P = 0.039), respectively., Conclusion: Galectin-1 and galectin-3 are overexpressed in RCC with different percentage in different subtypes. Galactin-1expression is more in tumor tissue than surrounding renal parenchyma suggesting that it has a carcinogenic role. Galectin-1 and galectin-3 overexpression in chromophobe RCC suggests that they may have diagnostic role., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Chyluria is usually associated with abnormal retrograde or collateral flow of lymph from intestinal lymphatics into lymphatics of the kidney, ureter or bladder. Chyluria has been described in patients with lymphoma, carcinoma, trauma, abscess, tuberculosis, filariasis, pregnancy and stenoses of the thoracic duct. In this case report we describe a patient who presented with chyluria associated with severe hyperlipidemia due to nephrotic syndrome induced by microscopic polyangiitis. Laboratory, histological and radiological examination did not show evidence of filarial infestation, tuberculous infection or malformation of the lymphatic system. Treatment with corticosteroids and cyclophosphamide resulted in improvement of hyperlipidemia and disappearance of chyluria.

Compression (or crushing) is used to induce nerve injury in test rats to study nerve degeneration and regeneration. The compression forces could be applied using a variety of techniques developed by several investigators. The lack of precise control of the applied compression may be the source of significant variations among observations. In this study, a Mosquito and dressing forceps were used. The Mosquito forceps was calibrated to determine the tip load corresponding to the clamping position. The dressing forceps was modified, instrumented with strain gauges and calibrated to directly measure the force applied at its tip. These two forceps were used to induce known and controlled nerve compression in 75 male Wistar rats (280-300g). The applied forces were of the order of 40N and 20N, for the Mosquito and dressing forceps, respectively.

We describe a patient who developed renal failure during antituberculous therapy. The condition was characterized by an initial phase of acute tubular necrosis and nephrotic syndrome which ultimately progressed to end-stage renal disease with severe interstitial fibrosis, despite adequate period of drug withdrawal. At that time, tuberculous infection was inactive and there was no evidence of amyloidosis or renal vein thrombosis.

Sensory innervation of lingual musculature was studied in young adult Wistar rats using retrograde labeling by horseradish peroxidase (HRP) and combined silver impregnation and acetylcholinesterase (AchE) methods. Intra-lingual injection of HRP resulted in labeling of neuronal somata in the trigeminal, superior vagal, and second cervical spinal (C2) ganglia. When HRP was directly applied to the proximal stump of severed hypoglossal nerve, labeling occurred only in the cervical and superior vagal ganglia. Morphometric analysis revealed that the labeled neurons were of the small-sized category in all ganglia. However, in the trigeminal and C2 ganglia, labeling occurred also among the medium-sized neurons. Combined silver and AchE preparations from lingual muscles revealed the absence of typical muscle spindles. Instead, there were free and spiral nerve terminals in the interstitium, and epilemmal knob-like or bouton-like endings surrounding non-encapsulated muscle fibers. These terminals showed AchE -ve reaction in contrast to the motor ones. Few ganglionic cells were scattered along the hypoglossal nerve with uniform AchE +ve reaction in their perikarya. This indicates that medium-sized neurons in the trigeminal and C2 ganglia, and probably sensory neurons along the hypoglossal nerve mediate lingual muscle sensibility perceived by atypical sensory terminals.

Pregnant squirrel monkeys were exposed to 2450-MHz (CW) microwaves at an equivalent power density of 10 mW/cm2 (SAR 3.4 mW/g) for three hours daily in a cavity-cage module. The exposure began when pregnancy was determined by a hormonal method, and continued through of offspring's first 9.5 months. After irradiation, the brain of the offspring were fixed with formaldehyde, and the inferior vermis of each cerebella was removed and processed for histologic observations. Purkinje cell density in the uvula was determined in sagittal serial section. There was no significant difference between control and experimental animals in the number of Purkinje cells per mm of Purkinje cell line (linear density), as well as in the density of Purkinje cells in the Purkinje cell layer.

The fiber connections between the trigeminal mesencephalic nucleus and tract and the trochlear nerve root of 15 cats were examined after silver impregnation of the pontomescencephalic region of the brains. The results revealed that: (a) some of the mesencephalic root fascicles join the trochlear root, (b) some of the mesencephalic root cells contribute their processes to the trochlear root, and (c) some mesencephalic cells are found amidst the fibers of the trochlear nerve during its intrabulbar course. The fibers of the trochlear nerve were counted at certain preselected sites before and after crossing the mesencephalic nucleus. The statistical data obtained indicated that the trigeminal mesencephalic root contributes 4-10% of the fibers of the trochlear nerve, before it crosses the mesencephalic nucleus.

The cerebella of 38 Sprague Dawley rats of various ages have been studied histologically by sectioning in certain parasagittal planes. The age groups were chosen from the early postnatal developmental stage (6, 11 and 16 days), around puberty (41, 46 and 51 days) and maturity (210 days). The sections yielded quantitative data with regard to the dimensions in parasagittal sections, of the entire cerebellum, the cerebellar cortex, the white core, the molecular layer and the granular layer, as well as, the differential and proportional growth of these layers at the above ages. The relative number of Purkinje cells per mm2 of sectional area of the cortex was also determined. The information presented in this study is of indicative value of the pattern of the growing cerebellum and of the ages in which the various layers and the relative number of Purkinje cells assume adult values.

In one experiment, Sprague Dawley rats (16-21 days of gestation) and their offspring were exposed to 100-MHz (CW) electromagnetic radiation at 46 mW/cm2 (SAR 2.77 mW/g) for 4 h/day for 97 days. In another experiment, the pregnant rats were irradiated daily from 17 to 21 days of gestation with 2450-MHz (CW) microwaves at 10 mW/cm2 (SAR 2 m W/G) for 21 h/day. In a third experiment, 6-day old rat pups were irradiated 7 h/day for five days with 2450-MHz radiation at 10 mW/cm2. Equal numbers of animals were sham irradiated in each group. Quantitative studies of Purkinje cells showed a significant and irreversible decrease in rats irradiated during fetal or fetal and early postnatal life. In animals exposed postnatally, and euthanized immediately after irradiation, significant decrease in the relative number of Purkinje cells was apparent. However, restoration apparently occurred after forty days of recovery.

The course of the great saphenous vein in a fascial canal derived from the deep fascia of the lower extremity is described. The fascial canal is absent in 15% of the cases. In 85% of the cases, the sheath surrounding the great saphenous vein is continuous from the thigh to the leg and supports the vein from the hydrostatic pressure of the blood, being absent only in the uppermost and the lowermost quarters of the vein in the thigh and the leg, respectively. Thus, up to one quarter of the vein is ensheathed in 30%, up to one half in 45% and up to three quarters in 10% of the cases studied. The absence of this fascial envelope of the vein, in whole or in part, may be involved in the pathogenesis or the complications of the varicosities of the great saphenous vein along with the well-known aggravating factors.