Peritoneal dialysis fluid activates calcium signaling and apoptosis in mesothelial cells.

A larger diffusion of peritoneal dialysis (PD) is limited by the progressive deterioration of the dialysis membrane structure and function, characterized in vitro and in vivo by mesothelial cell loss and closely related to the use of bioincompatible dialysis solutions. The apoptosis rate of rat and human mesothelial cells incubated in commercial PD fluid (PDF, 4.25 g/dL dextrose) became significant as early as 1 h after PDF addition and reached a plateau at 4-5 h. This pattern was unchanged after exposure to 1.5 g/dL dextrose PDF or freshly prepared PDF, indicating that effects were independent on the dextrose strength and manufacturing procedures but strictly dependent on PDF composition. Molecular studies revealed that PDF exposure inactivated the physiological volume recovery from hypertonic shrinkage, accompanied by an abnormal Ca(2+) signaling: a progressive intracellular Ca(2+) ([Ca(2+)](i)) rise resulting from an increased Ca(2+) entry. PDF also affected cytoskeleton integrity: early dissolution of actin filaments occurred well before the appearance of typical apoptosis features. Lastly, the PDF dependent apoptosis was almost completely prevented by the contemporary Ca(2+) concentration decrease and K(+) addition. This study suggests that the PDF dependent apoptosis arises from the extreme volume perturbations in mesothelial cells, turned out unable to regulate their volume back once exposed to a hyperosmolal medium containing high Ca(2+) levels in the absence of K(+), such PDF.

Double heterozygosity in the BRCA1 and BRCA2 genes in Italian family.

BACKGROUND: Double heterozygosity (DH) is an extremely rare event in which both BRCA1 and BRCA2 are mutated simultaneously in a family. To date, few cases of DH have been reported, especially in Ashkenazi populations. In Italy some cases of DH have been reported. In this study, we have described an Italian family with double heterozygosity in the BRCA genes. METHODS: The proband is a 43-year-old woman with bilateral breast cancer. She presented two pathogenic mutations in both BRCA genes, IVS8+2T>A (c.547+2T>A;p.Gln148Aspfsx51) in BRCA1, K944X (c.2830A>T;p.Lys944X) in BRCA2 and a novel variant IVS4-57A>G (c.426-57A>G) in BRCA2, not previously described. Both mutations were inherited from the paternal lineage in the proband's family. We investigated all available members of this family and we identified other two family members with DH. RESULTS AND CONCLUSIONS: Our observations support the hypothesis of a non-specific severe phenotype in DH carriers in terms of age of disease onset, cumulative lifetime risk and multiple primary tumours. Furthermore, our findings confirm that in order to identify all cases of DH, it is important not to limit the identification of mutations in a single gene, but extend the analysis to BRCA1 and BRCA2 and other breast cancer susceptibility genes.

Involvement of the ubiquitin-proteasome system in the formation of experimental postsurgical peritoneal adhesions.

We investigated the Ubiquitin-Proteasome System (UPS), major nonlysosomal intracellular protein degradation system, in the genesis of experimental postsurgical peritoneal adhesions. We assayed the levels of UPS within the adhered tissue along with the development of peritoneal adhesions and used the specific UPS inhibitor bortezomib in order to assess the effect of the UPS blockade on the peritoneal adhesions. We found a number of severe postsurgical peritoneal adhesions at day 5 after surgery increasing until day 10. In the adhered tissue an increased values of ubiquitin and the 20S proteasome subunit, NFkB, IL-6, TNF-α and decreased values of IkB-beta were found. In contrast, bortezomib-treated rats showed a decreased number of peritoneal adhesions, decreased values of ubiquitin and the 20S proteasome, NFkB, IL-6, TNF-α, and increased levels of IkB-beta in the adhered peritoneal tissue. The UPS system, therefore, is primarily involved in the formation of post-surgical peritoneal adhesions in rats.

Primary thyroid angiosarcoma: an unusual localization.

The finding of thyroid nodules is a very common occurrence in routine clinical practice. Approximately 5% to 7% of the entire population have thyroid nodules. Vascular lesions are one of the most controversial issues in thyroid pathology. These include benign lesions such as hemangiomas and, rarely, malignant tumors such as angiosarcomas or undifferentiated angiosarcomatoid carcinomas. In particular, angiosarcoma of the thyroid gland is a rare, highly aggressive malignant vascular tumor and in Italy the greatest geographical incidence of this lesion is witnessed near the Alps. Here, a case of thyroid angiosarcoma in a 71-year-old man with a history of goiter for about 20 years is described. The unusual localization of this lesion, the difficulties in reaching a definitive diagnosis for this particular histological type of primary tumor and a history of long-standing multinodular goiter in thyroid of an older man from outside the Alpine region prompted us to report this case of thyroid angiosarcoma mainly to discuss surgical, histopathological and immunohistochemical features.

Antibiotic prophylaxis in catheter-associated urinary infections.

This study aimed to assess the usefulness of antibiotic prophylaxis with Levofloxacin (LVFX) in short and mediumterm catheterisations. This study was developed to evaluate and confirm the effectiveness and need for prophylaxis in preventing catheter-associated UTIs, using LVFX at a dose of 250 mg administered orally to patients who had been subjected to short and medium-term urinary bladder catheterisation following surgery (3-14 days). The study was designed as a phase III study with parallel groups, multicentre, randomised, controlled with a placebo in three groups. The study was double-blind in treatment groups A and B and single-blind in group C. The study involved the recruitment of 120 patients, 40 for each treatment group. We show two types of results, one based on primary effectiveness variables and the other on the secondary effectiveness variables. The group treated with LVFX displayed a greater tendency toward the negativisation of bacteriuria and pyuria tests than that recorded for the placebo group, and was essentially comparable to that recorded for the group of patients treated with Ciprofloxacin. We can thus affirm that LVFX may be useful for preventing short and medium-term CAUTIs.

Benign thyroid disease: treatment notes.

AIM: The treatment of benign thyroid disease is a topic widely debated, ranging from "Lobectomy" to "Total Thyroidectomy". This study aims to contribute to the thinking on treatment strategies for benign thyroid disease. MATERIALS OF STUDY: Thirty five patients underwent surgical treatment following the pre-surgical diagnosis of benign thyroid disease between 2003 and 2005 at the Complex Unit of General and Geriatric Surgery at the Second University of Naples (S.U.N.). In 26 cases total thyroidectomies were performed, in 3 subtotal thyroidectomies, in 6 simple lobectomies. DISCUSSION: Post-surgical course was optimal in the majority of cases. The large number of total thyroidectomies performed is consistent with the trend favoured by this type of strategy. When backed by FNA, non-radical surgery can be opted with greater confidence for single nodules and when surgical risks are high. The refinement of surgical techniques and directions for the identifying and preparing the recurrent nerve have enabled a radical approach in treating thyroid nodular disease. CONCLUSIONS: In our opinion, for a solitary nodule with residual diseased parenchyma we believe total thyroidectomy should be prescribed. If, however, the residual parenchyma is unharmed a lobectomy may be considered. In conclusion, we recommend the individual assessment of each pathology, though we favour total thyroidectomy.

The sentinel lymph node: a suitable technique in breast cancer treatment?

AIM: The sentinel lymph node biopsy (SLNB) was firstly introduced by Giuliano and co. in 1994 for the treatment of breast cancer; in comparison to the axillary lymph node dissection (ALND), the sentinel lymph node biopsy has shown both a lower morbidity and acceptable distance results. We want to show that this technique is reliable and should be used routinely in selected cases. MATERIALS OF STUDY: The study on the sentinel lymph node has been carried out, prior informed consent, in 128 patients aged between 27 and 80 years and suffering from non-multicentric infiltrating breast carcinoma, with a diameter not greater than 3 cm, clinically negative axillary, and hospitalized from January 1998 to September 2005 at the Department of Gerontology, Geriatrics and Metabolic Diseases of the Second University of the Study of Naples. For the recruitment of patients subjected to the sentinel lymph node research study, we have respected the inclusion criteria. RESULTS: Histological examination of the tumor revealed 95 cases of ductal carcinoma, 16 cases of mucinus carcinoma, 13 of lobular carcinoma and 4 of medullary carcinoma. The sentinel lymph node was detected through lymphoscintigraphy in 96.9% of the cases (124 patients), whereas it was not possible to identify it in 4 patients (3.1% of the cases), 2 of which had previously been subject to excision biopsy. DISCUSSION: The SLNB is characterized by an identification rate of SLN > 90% with a false negative rate less than 5%. In our study we have found an SLN identification rate of 96.9% with false-negative rates of 3.9%. Our data show that in only 6,3% of the patients (4 non- identified and 4 false-negative cases) it was necessary to perform ALND because the SLN resulted positive; however no metastasis were observed in level III lymph nodes. CONCLUSIONS: Since its inception, the sentinel lymph node technique has gained an increasingly important role in the conservative treatment of the breast carcinoma due to the short duration of the surgery, the decrease of post-operative pain, the risk of lymphedema onset and hospital confinement, the high predictive power and the diagnostic accuracy. We strongly believe that the sentinel lymph node technique is reliable and should be used routinely in selected cases.

Our orientation regarding the ductal carcinoma in situ of the breast.

AIM: The ductal carcinoma in situ is a malignant proliferation of mammary ductal epithelial cells without invasion beyond the basement membrane. The management of patients with DCIS is complex, controversial and has undergone changes over time. MATERIAL OF STUDY: We treated 65 patients diagnosed with DCIS between 2002 and 2005. We surveyed women aged between 28 and 71 years (average age 51.4), the DCIS in 16 patients appeared as a palpable mass (about 2.2 cm) - group I and in 49 patients as microcalcifications detected on mammography - group II. RESULTS: The most frequent histological type was found to be the comedocarcinoma. After 3 years of follow-up, we had 3 cases of recurrence (4.6%) in patients undergoing conservative surgery, with Van Nuys Prognostic Index between 3 and 4. DISCUSSION: 15-25% of cases of breast cancer are DCIS. Most of these are comedocarcinomas. Comedo form DCIS is an insidious cancer. Surgical treatment ranges from mastectomy to excision of the lesion, often the latter, followed by radiotherapy. CONCLUSION: We prefer, with regard to surgical treatment, quadrantectomy with systematic control of the free margins. The search for the axillary sentinel node represents for us, too, the gold standard.

Clinical considerations on the retroperitoneal liposarcomas.

AIM: It presents a clinical case of undifferentiated retroperitoneal liposarcoma with 5 years' recurrence from the first operation for the rarity of the occurrence, the problems related to surgery and complementary therapeutic approach. MATERIAL OF STUDY: Male patient aged 73 was operated for removal of retroperitoneal mass with involvement of the right kidney at the Second University of Naples in the 2003. In accordance with the interdisciplinary board, complementary therapy is not indicated and follow-up program. The successive controls were negative until at least 2007. Reoperation for recurrence in 2008 for the presence of massive bone formation occupying a large part in the right half of the abdomen at the sub-hepatic level. In both cases histological examination showed undifferentiated liposarcoma. DISCUSSION: It is of unknown etiology and only 25% occurs in well-differentiated cells are also more than 100 histological subtypes, 85% are malignant. The most affected is the male sex and from the beginning looks like malignancy. The trend of growth in general is slow, and in most cases tends to recur over time. The role of chemotherapy and radiation therapy is controversial. CONCLUSIONS: The peculiarity of our case is higher than the average survival despite advanced age and presence of recurrence. This confirms the importance of surgical treatment, thus offering the patient a chance of better long-term survival.

The surgical treatment of benign breast lesions in young adolescents.

AIM: There is much controversy surrounding the treatment of benign breast lesions in young adolescents: on one side the need for surgical treatment and on the other doubts in regard to operating on young patients with a benign disease. Another element sparking the debate is the correlation between the appearance of fibroadenomas and the presence of elevated prolactin levels in the blood. MATERIAL OF STUDY: 42 patients between the ages of 14 and 21 being treated at the General surgery and Geriatrics Unit of the Department of Gerontology, Geriatrics and Metabolic Diseases at the Second University of Naples between 2001 and 2004. In addition, blood prolactin levels were measured in 24 patients. RESULTS: Only 4.76% of the patients examined (2 cases) had a family history of breast tumours. Out of a total of 42 adolescent patients that were operated on, we detected fibroadenomas in 35 (83.34%), fibrocystic disease in 3 (7.14%), adenosis in 3 patients (7.14%) and a phylloid tumour in 1 (2.38%). Blood prolactin was measured in 24 patients and in 17 cases we detected increased plasmatic levels of this hormone; in addition, anamneses revealed that of these 17 patients, 9 were using oral contraceptives. DISCUSSION: The most common cause of palpable breast masses in adolescents under 21 years of age are fibroadenomas. The connection to hormonal, genetic and family factors is still unknown, both during the genesis of this pathology and as concerns an increased risk of possible malignant development. The correlation between fibroadenomas and elevated prolactin serum levels still remains controversial today. Various studies, measuring the blood concentration of prolactin in many patients have demonstrated that both elevated blood levels of this hormone and the use of oral contraceptives play a role in the development and growth of benign breast lesions. CONCLUSION: Fortunately, breast disease is rare in adolescents; these patients do not often develop nodules and where these do occur the vast majority of cases involve benign lesions. A thorough follow-up on patients with nodular breast lesions is thus useful. As concerns the connection between prolactin and fibroadenomas, we also reported interesting data; this represents 70.83% of our subjects. KEYWORDS: Blood prolactin levels, Fibroadenomas, Surgical treatment.

Our experience of total mesorectal excision for rectal cancers.

BACKGROUND/AIMS: The total mesorectal excision (TME) for rectal tumours was introduced in 1982 by Heald et al. and has led both to a 5% de crease of local recurrences 5 and 10 years after the operation when compared with cases treated with conventional surgery, and to an increase of survival up to five years estimated in 80% of all cases. In Italy TME was firstly introduced for distal rectal carcinomas about 20 years ago, and has shown the same rate of local recurrences reported by Heald. The aim of our work is to highlight TME advantages and demonstrate how this more demanding and longer lasting method has an acceptable risk for the surgery of rectal tumours. METHODOLOGY: We have compared two groups of patients operated for rectal carcinoma; the first, "historical control group" (no TME, including 46 patients) was treated with the standard surgery technique, while the second group (TME, 47 patients) underwent the total mesorectal excision technique. 14 of non TME patients belonged to Dukes stage A, 20 to stage B and 12 to C; whereas in the TME group 16 patients belonged to Dukes stage A, 23 to B and 8 to C. The patients of both groups undergone the exams of follow up (blood test, hepatic ultrasonography, abdominal CT, thorax Ro); the follow up pattern included periodic controls with a check-up every three and six months, from one to five years. RESULTS: Postoperative complications in both groups do not show important differences in rates, although, the first group (no TME) had 11 cases with postoperative complications confronted with the 8 cases of the second group (TME). The complications taken into consideration were: anastomotic bleeding (3 patients no TME, 6% vs 1 patients TME, 2%), intestinal obstruction (1 patient no TME, 2% vs 1 patient TME, 2%), parietal infection (4 patients no TME, 9% vs 3 patients TME, 6%), anastomotic fistulae (2 patients no TME, 4% vs 2 patients TME, 4%), retention of urine and vesicular disorder (1 patient no TME, 2% vs 1 patient TME, 2%). Tumours closer to the anus have shown more complications compared with tumours at higher levels. As a matter of fact, 9 cases of no TME and TME patients with low located tumours have undergone complications compared with the 3 cases of no TME and TME patients with tumours being more distant from the anus; the rest 7 cases belonged to the middle rectum. A higher rate of local recurrences was noticed in the no TME group: 6 (13%) compared with the TME group: 3 (6%). Other tardy complications taken into consideration were: hepatic metastasis (5 patients no TME, 11% vs 4 patients TME, 8%), pulmonary metastasis (3, 6% of the no TME vs 2, 4% of the TME), anastomotic stenosis (4, 9% of the no TME vs 2, 4% of the TME), impotence (2, 4% of the no TME vs 1, 2% of the TME). We also noticed that most of the tardy complications in the TME group belonged to Dukes stage C. CONCLUSION: From our experience, we concluded that, in TME patients, complications are lower than in no TME patients; the site of the tumour affects the appearance of complications which are more frequently in distal localizations. An important result is the minor incidence of local recurrences after TME, which brings us to the conclusion that TME can be considered a valid method with an acceptable risk for the surgery of rectal tumour.

Congenital adrenal hyperplasia and Leydig cell tumor of testis. Case report and review of literature.

Adrenogenital Syndrome, more properly defined as Congenital Adrenal Hyperplasia (CAH), is related to the enzyme 21-beta-hydroxylase deficiency, with impaired glucocorticoids and aldosterone syntheses and increased ACTH synthesis. This report describes a case of a monorchid patient suffering from Adrenogenital Syndrome and Leydig cell tumor of his testis. A right orchidectomy with implantation of testis prosthesis was performed, after informing the patient on the consequences of his castration and obtaining his consent. Histology showed a testis measuring 4 x 3 x 2.5 cm with a 6 cm long spermatic cord; there was a yellowish, well-defined nodule measuring 3.5 x 1.5 cm, surrounded by normal parenchyma. This nodule had morphologic and immunohistochemical characteristics of a Leydig cell tumor, even found in the spermatic cord; those cells showed positivity to inibine, MART-1 and vimentine.

Solid-cystic pseudopapillary tumor of pancreas: description of two cases and literature review.

The authors report the cases of two young female patients aged 17 and 27 years who underwent surgery for a rare tumor of the pancreas, Frantz's tumor or solid-cystic pseudopapillary tumor. Solid-cystic pseudopapillary tumor of the pancreas is a rare tumor, accounting for 2.7% of pancreatic exocrine tumors. About 90% of these tumors occur in young women and they can reach very large dimensions. Due to their rareness and behavior, they are often associated with diagnostic and therapeutic problems. In most cases surgical treatment is curative and neither chemotherapy nor radiotherapy should be added. In the few cases where surgery is not possible, radiotherapy can be used because these tumors appear to be radiosensitive.

Hyperglycemia in streptozotocin-induced diabetic rat increases infarct size associated with low levels of myocardial HO-1 during ischemia/reperfusion.

This study investigated the role of heme oxygenase (HO)-1 in the cardiac tissue injury of acute ischemia/reperfusion (I/R) in diabetic streptozotocin (STZ)-induced hyperglycemic rats. The effects of 1) hemin, an inducer of HO expression and activity, and 2) zinc protoporphyrin IX (ZnPP-IX), an inhibitor of HO activity, have also been investigated on the tissue injury by I/R and some mediators released in these circumstances. STZ hyperglycemic rats had impaired levels of HO-1 within the cardiac tissue and increased myocardial infarct size (IS) following I/R, as compared with the nondiabetic rats. In these rats, administration of hemin 4 mg/kg 18 h before I/R increases the levels of HO-1 within the tissue. However, the values of HO-1 assayed in these circumstances were significantly lower (P < 0.01) than those assayed in nondiabetic animals subjected to the same procedures; IS was much more extended (P < 0.01) than in the parent nondiabetic group. STZ hyperglycemic rats also predisposed the heart to produce high levels of the cytokines interleukin (IL)-1beta and CXCL8. Subsequent I/R further increased (P < 0.01) the cytokine production, an effect partly prevented by hemin treatment. This recovered the huge number of infiltrated polymorphonuclear (PMN) leukocytes within the cardiac tissue associated with the STZ hyperglycemic state and I/R damage.

Outcome of surgical treatment of carcinoma of the pancreas.

AIMS AND BACKGROUND: Pancreatic resections for neoplastic diseases have a high risk of severe intra- and postoperative complications and are associated with high mortality rates. They should be performed as a rule in centers specializing in this type of surgery. However, it is becoming increasingly likely that such tumors may have to be treated in surgery units which are not specifically dedicated to pancreatic surgery. The aim of this study was to assess the improvements in clinical results in a non-specialized general surgery setting in the light of the most recent progress in surgical techniques, drug treatments and nutritional support. METHODS AND STUDY DESIGN: We analyzed 48 patients with pancreatic cancer treated in our institution over the period from 1980 to 1998: 36 had cancer of the head of the pancreas, 5 of the ampulla, 1 in the second duodenal portion, and 6 of the body-tail. The operations performed consisted of 13 Whipple pancreaticoduodenectomies with cutting and stapling of the distal pancreatic stump at the level of the isthmus, 4 left pancreasectomies, 2 local resections of the ampulla, 21 palliative operations, and 2 exploratory laparotomies. RESULTS AND CONCLUSIONS: The patients were submitted to follow-up including clinical examinations, blood-chemistry tests, and instrumental investigations. The mean survival was 18 months in the cases where radical surgery was performed, compared to 11 months after palliative surgery. We conclude that an improved prognosis can obtain after pancreatic resection. This is attributable to a more accurate preoperative staging and to the aid of the various forms of nutritional support and pharmacological prophylaxis currently available.

[Outpatient parenteral antibiotic therapy (OPAT) of diabetic foot infections with piperacillin/tazobactam]. / Terapia iniettiva domiciliare delle infezioni del piede diabetico con piperacillina/tazobactam.

Treatment of diabetic foot infections (DFIs) represents an important challenge for surgeons, especially in light of the poor results achieved by traditional therapeutic approaches. In this study, the clinical and bacteriological efficacy of TZP for treatment of DFIs in 38 outpatients was evaluated. All patients (median age 63 yrs) were affected by DFIs to different degrees of severity according to Wagner's classification: degree 0, 7 pts; degree 1, 17 pts; degree 2, 10 pts; degree 3, 4 pts. Degree 0-1 infections underwent a 10-18 day course with TZP given i.m. (2.25 g bid); degree 2-3 infections were initially treated with TZP i.v. (4.5 g bid or tid). Some patients began treatment in hospital and after early discharge continued parenteral therapy at home; others were treated exclusively at home. Some pts, after a 5-7-day course of i.v. therapy switched to i.m. route. The average duration of antibiotic therapy was 28 days. At the end of treatment with TZP, some patients underwent a new treatment with oral coamoxi-clav for 10-15 days. A bacteriological examination was done for all patients: ulcus (degree 1) and deep tissue (degree 2-3) swabs at the first surgical toilette. Clinical controls, medications, surgical toilettes and microbiological cultures were performed according to the degree of severity, extension of the lesion and response to treatment. All cultures were positive for polymicrobial infections (Staphylococcus spp, Enterococcus spp, Enterobacteriaceae, Pseudomonas spp). In 30/38 pts (79%) a complete resolution was observed; in 4 pts (10%) an improvement. DFIs require long term parenteral treatment, with wide spectrum antibiotics including Gram +, Gram - and anaerobes. OPAT represents a valid alternative to hospitalisation when the general conditions of the patient are stable, the infection is not too severe and complications are not present. TZP proved to be a good choice for treatment of diabetic foot infections that, due to its high safety, can be successfully utilized also in OPAT programmes

Spigelian hernia: a rare lateral ventral hernia.

The authors take a treated clinical case as a starting point to consider lateral ventral hernia, generally referred to as "Spigelian hernia". Such hernias are rare (1-2% of all hernias), with a slightly higher incidence in the female sex. Obesity and multiparous status are known to be predisposing factors. Instrumental tests of great importance in terms of specificity and definition such as ultrasonography and computed tomography are available, in cases of diagnostic doubt, for a pathology that in any case has to be detected early in order to avoid possible complications. The treatment is essentially surgical. A personal variant of the surgical repair technique is described with the use of prosthetic material, which guarantees a better result in terms of strength and resistance compared to simple repair surgery.

[Peritoneal multicystic mesothelioma: unusual case of localization in the left lobe of the liver]. / Mesotelioma multicistico del peritoneo: un caso insolito localizzato al lobo sinistro del fegato.

Peritoneal multicystic mesothelioma is a very rare clinical condition. This neoplastic variant has a high incidence of recurrence after surgical resection. It usually occurs in middle-aged women with a previous history of gynaecological surgery and presents with the symptoms of an abdominal or pelvic mass. The case reported here is that of a 58-year-old woman, characterised first by a left liver-lobe tumour and then by a subsequent episode of emission of cystic matter from an abdominal fistula. The relevant literature is reviewed and the clinical aspects and treatment of this disease are discussed.

Dipeptidyl peptidase 4 inhibition may facilitate healing of chronic foot ulcers in patients with type 2 diabetes.

The pathophysiology of chronic diabetic ulcers is complex and still incompletely understood, both micro- and macroangiopathy strongly contribute to the development and delayed healing of diabetic wounds, through an impaired tissue feeding and response to ischemia. With adequate treatment, some ulcers may last only weeks; however, many ulcers are difficult to treat and may last months, in certain cases years; 19-35% of ulcers are reported as nonhealing. As no efficient therapy is available, it is a high priority to develop new strategies for treatment of this devastating complication. Because experimental and pathological studies suggest that incretin hormone glucagon-like peptide-1 may improves VEGF generation and promote the upregulation of HIF-1α through a reduction of oxidative stress, the study evaluated the effect of the augmentation of GLP-1, by inhibitors of the dipeptidyl peptidase-4, such as vildagliptin, on angiogenesis process and wound healing in diabetic chronic ulcers. Although elucidation of the pathophysiologic importance of these aspects awaits further confirmations, the present study evidences an additional aspect of how DPP-4 inhibition might contribute to improved ulcer outcome.

Peri-procedural tight glycemic control during early percutaneous coronary intervention is associated with a lower rate of in-stent restenosis in patients with acute ST-elevation myocardial infarction.

OBJECTIVE: We examined the effects of peri-procedural intensive glycemic control (IGC) during early percutaneous coronary intervention (PCI) on restenosis rate in hyperglycemic patients with ST-segment elevation myocardial infarction (STEMI). RESEARCH DESIGN AND METHODS: A total of 165 hyperglycemic patients (glucose ≥ 140 mg/dl) with first STEMI undergoing PCI were studied. Patients were randomized to IGC for almost 24 h after PCI (n = 82; glucose, 80-140 mg/dl) followed by multidose sc insulin during the hospital stay or conventional glycemic control (CGC; n = 83; glucose, 180-200 mg/dl) followed by conventional therapy. Coronary angiography was performed at study entry and at 6-month follow-up. Blood samples for glycemia, hemoglobin A1c, inflammatory markers (C-reactive protein and TNF-α), monocyte chemoattractant-protein-1, and oxidative stress (nitrotyrosine) were collected immediately before and 24 h, 30 and 180 d after PCI. RESULTS: After insulin infusion, mean plasma glucose during the peri-procedural period was greater in the CGC group than in the IGC group (CGC, 191 ± 15 mg/dl; IGC, 145 ± 35 mg/dl; P < 0.001). After the insulin infusion period, the levels of markers of oxidative stress (nitrotyrosine), inflammation (C-reactive protein, TNF-α), and monocyte chemoattractant-protein-1 were significantly higher in CGC patients compared with IGC patients. Moreover, ICG during PCI reduces restenosis by half (48 and 24%) at 6 months. During follow-up, there was no difference in mortality rates, glucose, inflammatory and oxidative stress markers among the groups. In-stent restenosis was positively associated with mean plasma glucose levels as well as oxidative stress and inflammatory markers during the insulin infusion period. CONCLUSIONS: In hyperglycemic patients with STEMI, optimal peri-procedural glycemic control by reducing oxidative stress and inflammation may improve the outcome after PCI.