Somatostatin receptor 1–5; expression profiles during rat development

Background

Somatostatin acts through five receptor subtypes (SSTRs 1–5). We aimed to investigate SSTRs mRNA expression and protein distribution in whole rat embryos, with special emphasis on the pancreas.

Material and methods

Rat embryos were collected on embryonal days 10, 11, 12, 14, 15, 17, 19, 21, and at birth. Presence of SSTRs was investigated with RT-PCR techniques and immunohistochemistry.

Results

There was no SSTR5 mRNA expression in the whole rat embryos. All SSTR1–5 proteins were observed at embryonal day 10, but the localization varied between the different subtypes. From day 11 to birth SSTRs protein presence increased with time in major structures such as skin and cartilage. It remained similar over time in the heart and liver. In the fetal pancreas mRNA expression of SSTR2 and 4 was detected at day 14, and there was an increase up to birth. Only SSTR1 protein co-localized to a higher extent with the islet hormones studied. SSTR2 was present in all islet endocrine cells except for β-cells. In contrast, the immunostaining for SSTR3–4 was co-localized with insulin and PP, and, finally, SSTR5 with glucagon and pancreatic polypeptide. In mRNA isolated from whole rat embryos SSTR1-2 and SSTR4 expression showed a peak at day 14, while SSTR3 mRNA was not present until day 15.

Conclusion

The present data suggest a role for SSTRs during the development of the rat embryo. Subsequent functional studies may elucidate regulatory roles of specific SSTRs for the growth and differentiation of the pancreas as well as other organs.     

Adipokines and proinflammatory cytokines,the key mediators in the pathogenesis of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The “two-hit“ hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.     

Case Report: Cutaneous Leishmaniasis in Cuban Immigrants to Texas who Traveled through the Darién Jungle,Panama

Cutaneous leishmaniasis is rarely seen in the United States. Four Cuban immigrants traveled along the same route at different times from Cuba to Ecuador, then northward, including through the Darién Jungle in Panama. These patients had chronic ulcerative non-healing skin lesions and were given a diagnosis of leishmaniasis.Leishmaniasis is a vector-borne disease caused by the protozoan parasite of the genus Leishmania and is spread by the bite of sand flies from the sub-family Phlebotominae.¹ There are various clinical manifestations of leishmaniasis, including cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis, and visceral leishmaniasis. Cutaneous leishmaniasis occurs at the site of the bite, with lesions forming weeks to months later starting with a papule, which then develops into a nodule or plaque-like lesion and progresses to a painless ulceration with an indurated border.We report four cases of CL caused by Leishmania (Viannia) panamensis in Cuban immigrants who traveled through the Darién Gap Jungle between Colombia and Panama on their journey north to the United States. This region has been shown to have high transmission rates of leishmaniasis,² and, in 2012, Panama experienced an outbreak beyond expected endemic rates.³ This case series highlights a previously underappreciated immigration route to the United States for Cubans and the need to include leishmaniasis as a differential diagnosis for non-healing skin ulcers in this patient population.During May 2012–April 2013, four persons who had recently immigrated to the United States from Cuba came to the National School of Tropical Medicine at Baylor College of Medicine''s (BCM) Tropical Medicine Clinic for non-healing skin ulcers. All four persons reported a similar route of travel from Cuba to Texas (Figure 1), although at different times. Each person began their journey by flying to Quito, Ecuador, where they then traveled by bus through Colombia, passing through the cities of Pasto and Cali to Quibdo. In Quibdo, they took a short flight to Bahia Solano, Colombia, where a boat ride then transported them to Punta Ardita near the Panama border. They then traveled by foot through the thick jungle in Darién, Panama, for 5–15 days. During this time, they slept outdoors and reported numerous insect bites. Once through the Darién area, they traveled northward until they entered the United States at the Mexican border.Open in a separate windowFigure 1.Map showing immigration route of a cluster of Cuban patients with cutaneous leishmaniasis caused by Leishmania (V.) panamensis. Note the travel by foot through the thick jungle of the Darién National Park, Panama, where they likely contracted the disease.Once in the United States, the four persons sought medical care at outside clinics for skin lesions that had developed within two months after they passed though the Darién. They were treated for presumed infection with Staphylococcus aureus. The antibiotics had no therapeutic effect, and the lesions continued to grow and develop into non-healing, painless ulcers with accompanying satellite lesions. Once in Houston, Texas, the four persons were directed to the Department of Dermatology at BCM (

Macrophage mineralocorticoid receptor signaling plays a key role in aldosterone-independent cardiac fibrosis

Mineralocorticoid receptor (MR) activation promotes the development of cardiac fibrosis and heart failure. Clinical evidence demonstrates that MR antagonism is protective even when plasma aldosterone levels are not increased. We hypothesize that MR activation in macrophages drives the profibrotic phenotype in the heart even when aldosterone levels are not elevated. The aim of the present study was to establish the role of macrophage MR signaling in mediating cardiac tissue remodeling caused by nitric oxide (NO) deficiency, a mineralocorticoid-independent insult. Male wild-type (MRflox/flox) and macrophage MR-knockout (MRflox/flox/LysMCre/+; mac-MRKO) mice were uninephrectomized, maintained on 0.9% NaCl drinking solution, with either vehicle (control) or the nitric oxide synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (L-NAME; 150 mg/kg/d) for 8 wk. NO deficiency increased systolic blood pressure at 4 wk in wild-type L-NAME/salt-treated mice compared with all other groups. At 8 wk, systolic blood pressure was increased above control in both L-NAME/salt treated wild-type and mac-MRKO mice by approximately 28 mm Hg by L-NAME/salt. Recruitment of macrophages was increased 2- to 3-fold in both L-NAME/salt treated wild-type and mac-MRKO. Inducible NOS positive macrophage infiltration and TNFα mRNA expression was greater in wild-type L-NAME/salt-treated mice compared with mac-MRKO, demonstrating that loss of MR reduces M1 phenotype. mRNA levels for markers of vascular inflammation and oxidative stress (NADPH oxidase 2, p22phox, intercellular adhesion molecule-1, G protein-coupled chemokine receptor 5) were similar in treated wild-type and mac-MRKO mice compared with control groups. In contrast, L-NAME/salt treatment increased interstitial collagen deposition in wild-type by about 33% but not in mac-MRKO mice. mRNA levels for connective tissue growth factor and collagen III were also increased above control treatment in wild-type (1.931 ± 0.215 vs. 1 ± 0.073) but not mac-MRKO mice (1.403 ± 0.150 vs. 1.286 ± 0.255). These data demonstrate that macrophage MR are necessary for the translation of inflammation and oxidative stress into interstitial and perivascular fibrosis after NO deficiency, even when plasma aldosterone is not elevated.     

Bone morphogenetic protein- and mating-dependent secretory cell growth and migration in the Drosophila accessory gland

The paired male accessory glands of Drosophila melanogaster enhance sperm function, stimulate egg production, and reduce female receptivity to other males by releasing a complex mixture of glycoproteins from a secretory epithelium into seminal fluid. A small subpopulation of about 40 specialized secretory cells, called secondary cells, resides at the distal tip of each gland. We show that these cells grow via mechanisms promoted by mating. If aging males mate repeatedly, a subset of these cells delaminates from and migrates along the apical surface of the glandular epithelium toward the proximal end of the gland. Remarkably, these secretory cells can transfer to females with sperm during mating. The frequency of this event increases with age, so that more than 50% of triple-mated, 18-d-old males transfer secondary cells to females. Bone morphogenetic protein signaling specifically in secondary cells is needed to drive all of these processes and is required for the accessory gland to produce its normal effects on female postmating behavior in multiply mated males. We conclude that secondary cells are secretory cells with unusual migratory properties that can allow them to be transferred to females, and that these properties are a consequence of signaling that is required for secondary cells to maintain their normal reproductive functions as males age and mate.     

The effect of calcium ion concentration on the bone response to oxidized titanium implants

Aim: To investigate the effect of calcium concentration on the bone tissue response to Ca‐incorporated titanium implants Materials and methods: Two titanium surfaces containing 4.2% and 6.6% calcium were prepared using the micro‐arc oxidation process. The implants were inserted in the tibia of nine New Zealand White rabbits. After 6 weeks of healing, the bone response to the implants was quantitatively compared by biomechanical and histomorphometrical measurements. Results: Ca 4.2% and Ca 6.6% containing implants revealed no distinctive differences in their qualitative surface chemistry; chemical bonding state of Ca in titanium oxide was mainly calcium titanates. No significant differences were observed between two implants in peak removal torque and shear strength comparisons (P>0.05). Histomorphometrical analyses presented no significant differences in bone–metal contact, bone area and newly formed bone measurements between two implants (P>0.05). Conclusions: From biomechanical and histomorphometrical measurements, the two calcium concentrations in this study did not differ significantly with respect to their influence on the bone tissue response. This similar bone response in rabbit tibiae may be explained by the similarity of the qualitative Ca chemistry in titanium surfaces.