Transdifferentiation of both intra- and extra-islet cells into beta cells in nicotinamide treated neonatal diabetic rats: An in situ hybridization and double immunohistochemical study

We aimed to study the effect of nicotinamide (NA) on beta (beta)-cell regeneration and apoptosis in streptozotocin induced neonatal rats (n-STZ). Three groups were performed: Control group, n2-STZ group (100 mg/kg STZ on the second day-after birth), n2-STZ + NA group (STZ;100 mg/kg + NA;500 mg/kg/day for 5 days). The pancreatic tissue sections were immunostained with insulin, glucagon, somatostatin, Pdx1, Notch1 and active caspase-3 antibodies, and double immunostained with insulin/PCNA, insulin/glucagon and insulin/somatostatin antibodies. In situ hybridization carried out with insulin probe. Apoptotic beta-cell were shown by TUNEL assay, followed by immunostaining. The number of insulin/PCNA, insulin/glucagon and insulin/somatostatin double-positive cells significantly increased in n2-STZ + NA group compared with the other groups (p < 0.001). n2-STZ group had lower number of insulin and Pdx1 positive cells in islets, compared to NA treated diabetics. The insulin and Pdx1 immun positive cells were located in the small clusters or scattered through the exocrine tissue and around to ducts in n2-STZ + NA group. Notch1 positive cell numbers were increased, whereas caspase-3 and TUNEL positive beta-cell numbers were decreased in n2-STZ + NA group. NA treatment induces the neogenic insulin positive islets orginated from the differentiation of ductal progenitor cells, transdifferentiation of acinar cells into beta cells, and transformation of potent precursor cells and centroacinar cells via the activated Notch expression into beta-cells in n-STZ rats

The role of clusterin on pancreatic beta cell regeneration after exendin-4 treatment in neonatal streptozotocin administrated rats

We investigated the effects of exendin-4 (Ex4) treatment on expression of clusterin and beta cell regeneration in the endocrine pancreas in neonatal streptozotocin (nSTZ) diabetic rats. Three groups were used: (1) n2-STZ group; on the second day after birth 100 mg/kg STZ was given i.p. to two groups of newborn rats, (2) n2-STZ+Ex4 group; 3 mu g/kg/day Ex4 was given for 5 days starting on the third day, and (3) control group. In situ hybridization for mRNAs of insulin and clusterin, double immunostaining for insulin/clusterin and insulin/BrdU were carried out. Immunostaining for insulin, glucagon, somatostatin, clusterin, synaptophysin and pdx-1 was performed. In the n2-STZ + Ex4 group, BrdU/insulin and insulin/clusterin immunopositive cells were significantly increased in the islets of Langerhans in comparison to the other groups. The areas occupied by the insulin mRNA and peptide positive cells and also pdx-1 immunopositive cells were decreased in the n2-STZ diabetic group compared with the other groups. The clusterin mRNA and protein positive cells, and also the glucagon and somatostatin cells, were significantly increased in the islets of the n2-STZ and the n2-STZ + Ex4 groups compared with the control group. The results show that Ex4 treatment induces new beta cell clusters via up-regulation of clusterin, which might be effective on beta-cell proliferation and neogenesis. (C) 2012 Elsevier GmbH. All rights reserved

The effects of alpha lipoic acid on liver cells damages and apoptosis induced by polyunsaturated fatty acids

&Ouml;ze

Obestatin and insulin in pancreas of newborn diabetic rats treated with exogenous ghrelin

The aim of the study was to evaluate the effect of ghrelin treatment on obestatin, insulin gene expression and biochemical parameters in the pancreas of newborn-streptozocin (STZ) diabetic rats. Rats were divided into 4 groups. Group I: control rats treated with physiological saline; group II: control rats treated with 100 mu g/kg/day ghrelin; group III: two days after birth rats that received 100 mg/kg STZ injected as a single dose to induce neonatal diabetes; group IV: neonatal-STZ-diabetic rats treated with ghrelin for four weeks. Sections of the pancreas were examined with immunohistochemistry for the expression of obestatin and insulin and in situ hybridization for the expression of insulin mRNA. The blood glucose levels were measured. Tissue homogenates were used for protein, glutathione, lipid peroxidation and non-enzymatic glycosylation levels and antioxidant enzyme analysis. There was a significant difference in blood glucose levels in newborn-STZ-diabetic rats compared to ghrelin treated diabetic rats at weeks 1, 2 and 4. In group IV, pancreatic non-enzymatic glycosylation and lipid peroxidation levels were decreased, however, glutathione levels and enzymatic activities were increased. Insulin peptide and mRNA (+) signals in islets of Langerhans and obestatin immunopositive cell numbers showed an increase in group IV compared to group III. These results suggest that administration of ghrelin to newborn rats may prevent effects of diabetes. (C) 2011 Published by Elsevier GmbH

Analysis of Inflammatory Cells with Immunuhistochemical Method in Bronchoalveolar Lavage Fluids of Sarcoidosis Patients

Sar ko i doz pa to ge ne zi iyi bi lin me yen sis te mik bir has ta lık tır. Ol gu la rın %50&rsquo;sin de ak ci ğer tu tu lu - mu g&ouml; r&uuml; l&uuml;r. Pul mo ner sar ko i doz la bir lik te g&ouml; r&uuml; len kon trol s&uuml;z T h&uuml;c re si pro li fe ras yo nu ve za rar lı kim ya sal medi ya t&ouml;r le rin sa lın ma sı gi bi pa to lo jik olay lar im m&uuml; no lo jik me ka niz ma lar ile a&ccedil;ık la na bi lir. Pul mo ner sar ko i doz da Th1 si to kin le ri nin ve mak ro faj ak ti vas yo nu ile il gi li si to kin le rin su nu mu nun ter cih edil di ği ni g&ouml;s te ren &ccedil;a lış malar mev cut ol mak la bir lik te, si to kin su nu mu ko nu sun da ye te rin ce &ccedil;a lı şıl ma mış tır. Bu &ccedil;a lış ma da, sar ko i doz lu has ta la rın ak ci ğer le rin de g&ouml; r&uuml; len yan gı sal olay la rın baş la ma sı ve de va mın dan so rum lu olan h&uuml;c re tip le ri ni ve bu yan gı sal re ak si yon la rı y&ouml;n len dir me de &ouml;nem li ola bi le cek si to kin le rin su nu mu nu araş tır ma yı ama&ccedil; la dık. Ge - re&ccedil; ve Y&ouml;n tem ler: &Ccedil;a lış ma da 7 sar ko i doz lu has ta ile 7 sağ lık lı kon trol den alı nan bron ko al ve o lar la vaj (BAL) sıvı sın dan si to san tr&uuml; f&uuml;j de ha zır la nan pre pa rat lar kul la nıl dı. T&uuml;m &ouml;r nek le re CD4 ve CD8 mo nok lo nal an ti kor la rı ile im m&uuml;n bo ya ma ya pı la rak T h&uuml;c re si alt tip le ri nin da ğı lı mı araş tı rıl dı. Ay rı ca T yar dım cı-1(Th1) ti pi si to kinler den olan in ter fe ron ga ma (IFN&gamma;) ve bir mak ro faj be lir te ci olan CD68 eks pres yo nu da im m&uuml; no his to kim ya sal ola rak in ce len di. Bul gu lar: Sar ko i doz lu has ta la rın BAL sı vı la rın dan ha zır la nan si to san tri f&uuml;j pre pa rat la rın da len - fo sit sa yı sın da sağ lık lı kon trol gru bu na kı yas la an lam lı (p=0,002) bir ar tış sap tan dı. T len fo si ti alt grup la rı nın ince len me si so nu cun da CD4(+) yar dım cı T h&uuml;c re le ri nin (Th) (%21,59&plusmn;0,87) CD8(+) bas kı la yı cı T h&uuml;c re le ri ne (Ts) (%10,40&plusmn;0,59) kı yas la &ccedil;o ğun luk ta ol du ğu g&ouml;z len di. Th/Ts (CD4+/CD8+) ora nı sar ko i doz gru bun da 2/1 ola rak sap tan dı. Sar ko i doz lu has ta la rın BAL pre pa rat la rın da IFN&gamma; su nu mu ya pan T h&uuml;c re le ri ne rast lan dı. CD68 su nu - mu, sar ko i doz lu grup ta ki mak ro faj la rın ya nı sı ra, ba zı dev h&uuml;c re ler, len fo sit ler ve po li morf n&uuml; ve li l&ouml; ko sit ler de de g&ouml; r&uuml;l d&uuml;. So nu&ccedil;: Bul gu la rı mız, yar dım cı T len fo sit ler de ki ar tı şın, sar ko i doz pa to ge ne zi ne ka tı lan &ouml;nem li bir fak t&ouml;r ol du ğu nu ve art mış len fo sit le rin Th1 ti pi si to kin le rin su nu mu nu ter cih et ti ği ni g&ouml;s ter mek te dir

Analysis of Inflammatory Cells with Immunuhistochemical Method in Bronchoalveolar Lavage Fluids of Sarcoidosis Patients

Sar ko i doz pa to ge ne zi iyi bi lin me yen sis te mik bir has ta lık tır. Ol gu la rın %50&rsquo;sin de ak ci ğer tu tu lu - mu g&ouml; r&uuml; l&uuml;r. Pul mo ner sar ko i doz la bir lik te g&ouml; r&uuml; len kon trol s&uuml;z T h&uuml;c re si pro li fe ras yo nu ve za rar lı kim ya sal medi ya t&ouml;r le rin sa lın ma sı gi bi pa to lo jik olay lar im m&uuml; no lo jik me ka niz ma lar ile a&ccedil;ık la na bi lir. Pul mo ner sar ko i doz da Th1 si to kin le ri nin ve mak ro faj ak ti vas yo nu ile il gi li si to kin le rin su nu mu nun ter cih edil di ği ni g&ouml;s te ren &ccedil;a lış malar mev cut ol mak la bir lik te, si to kin su nu mu ko nu sun da ye te rin ce &ccedil;a lı şıl ma mış tır. Bu &ccedil;a lış ma da, sar ko i doz lu has ta la rın ak ci ğer le rin de g&ouml; r&uuml; len yan gı sal olay la rın baş la ma sı ve de va mın dan so rum lu olan h&uuml;c re tip le ri ni ve bu yan gı sal re ak si yon la rı y&ouml;n len dir me de &ouml;nem li ola bi le cek si to kin le rin su nu mu nu araş tır ma yı ama&ccedil; la dık. Ge - re&ccedil; ve Y&ouml;n tem ler: &Ccedil;a lış ma da 7 sar ko i doz lu has ta ile 7 sağ lık lı kon trol den alı nan bron ko al ve o lar la vaj (BAL) sıvı sın dan si to san tr&uuml; f&uuml;j de ha zır la nan pre pa rat lar kul la nıl dı. T&uuml;m &ouml;r nek le re CD4 ve CD8 mo nok lo nal an ti kor la rı ile im m&uuml;n bo ya ma ya pı la rak T h&uuml;c re si alt tip le ri nin da ğı lı mı araş tı rıl dı. Ay rı ca T yar dım cı-1(Th1) ti pi si to kinler den olan in ter fe ron ga ma (IFN&gamma;) ve bir mak ro faj be lir te ci olan CD68 eks pres yo nu da im m&uuml; no his to kim ya sal ola rak in ce len di. Bul gu lar: Sar ko i doz lu has ta la rın BAL sı vı la rın dan ha zır la nan si to san tri f&uuml;j pre pa rat la rın da len - fo sit sa yı sın da sağ lık lı kon trol gru bu na kı yas la an lam lı (p=0,002) bir ar tış sap tan dı. T len fo si ti alt grup la rı nın ince len me si so nu cun da CD4(+) yar dım cı T h&uuml;c re le ri nin (Th) (%21,59&plusmn;0,87) CD8(+) bas kı la yı cı T h&uuml;c re le ri ne (Ts) (%10,40&plusmn;0,59) kı yas la &ccedil;o ğun luk ta ol du ğu g&ouml;z len di. Th/Ts (CD4+/CD8+) ora nı sar ko i doz gru bun da 2/1 ola rak sap tan dı. Sar ko i doz lu has ta la rın BAL pre pa rat la rın da IFN&gamma; su nu mu ya pan T h&uuml;c re le ri ne rast lan dı. CD68 su nu - mu, sar ko i doz lu grup ta ki mak ro faj la rın ya nı sı ra, ba zı dev h&uuml;c re ler, len fo sit ler ve po li morf n&uuml; ve li l&ouml; ko sit ler de de g&ouml; r&uuml;l d&uuml;. So nu&ccedil;: Bul gu la rı mız, yar dım cı T len fo sit ler de ki ar tı şın, sar ko i doz pa to ge ne zi ne ka tı lan &ouml;nem li bir fak t&ouml;r ol du ğu nu ve art mış len fo sit le rin Th1 ti pi si to kin le rin su nu mu nu ter cih et ti ği ni g&ouml;s ter mek te dir