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2.
Arch Ital Urol Androl ; 86(2): 118-22, 2014 Jun 30.
Article in English | MEDLINE | ID: mdl-25017592

ABSTRACT

AIM OF THE STUDY: To demonstrate how, in a center with a large number of patients, as our center is, it is possible to perform ureterolithotripsy using a limited set of instruments. METHODS: We evaluated medical charts of our center related to semirigid ureteral ureteroscopy (URS) with ureterolithotripsy using Holmium laser performed from July 2004 to July 2011. Overall, 658 URS for ureteral stones were performed in 601 patients, of which 204 in proximal ureter (31%), 86 in the mid (13.06%) and 368 (57.76%) in the distal ureter. In 504 patients (76.5%) ureterohydronephrosis (Grade II-III) was observed. In 57 patients (8.6%), we performed a bilateral approach at the same time, but most patients had a solitary distal ureteral stone. 106 patients (16.1%) had more than one stone in their distal ureter and 96 (14.8%) had a proximal ureteral stone treated in the same surgery as well. RESULTS: The overall stone-free rate for ureteral stones was 86.1% (567/658). Success rates for proximal, medial and distal ureteral stones were 68.13% (139/204 patients), 84.8% (73/86 patients) and 96.4% (355/368 patients), respectively. One hundred and twenty patients (18.3%) required additional surgical treatment for their stones beyond the initial URS, including a second URS in 97 patients (14.74%) and URS plus Retrograde Intra-Renal Surgery (RIRS) in 23 patients (3.54%). The overall stonefree rate after the second treatment was 99.3%. Intra-operative complications accounted for 5.92% and consisted of ureteral perforations in 16 pts (2.4%), erosions of urothelium leading to significant bleeding in 15 pts (2.27%), severe pain in 4 pts (0.6%), fever in 3 pts (0.45%) and one case of ureteral avulsion (0.15%). CONCLUSIONS: This study demonstrates that the use of Holmium laser lithotripsy is a safe and effective means of treating ureteral stones regardless of sex, age, stone location, or stone size. The instrumentation we used was extremely limited, in order to reduce costs related to the procedure to an absolute minimum whilst maintaining the two quality indicators for the procedure, namely success rate and length of hospitalisation (86.1% and 34 hours).


Subject(s)
Lithotripsy , Ureteral Calculi/therapy , Ureteroscopes , Ureteroscopy/economics , Costs and Cost Analysis , Equipment Design , Humans
3.
Arch Ital Urol Androl ; 85(2): 86-91, 2013 Jun 24.
Article in English | MEDLINE | ID: mdl-23820656

ABSTRACT

OBJECTIVE: Transurethral resection of the prostate (TURP) is the current optimal thera- py for the relief of bladder outflow obstruction, with subjective and objective success rate of 85 to 90%. Aim of this study was to evaluate efficacy and safety of Plasmakinetic ener- gy (Gyrus electro surgical system), which produces vaporization of tissue immersed in isotonic saline against standard monopolar transurethral resection of the prostate. METHODS: From January 2002 to April 2002, 160 consecutive patients, who had low urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH) were enrolled in this study. Patients were randomised to undergo bipolar TURP (80 patients) or monopolar TURP (80 patients). Preoperative work-up was assessed by administering IPSS, IIEF-5 and Qol questionnaires. All patients were submitted to uroflowmetry, transrectal ultrasound (TRUS), post-voidal residual urine measurement and PSA determination. In the two groups, IPSS, IIEF-5 and Qol, uroflowme- try, TRUS, post-voidal residual urine measurement, PSA determination and number of reopera- tions were evaluated at 1, 3, 6, 12, 18, 24, 30 and 36 months follow up, and then every year. Furthermore, in both groups operative time, resected tissue weight and perioperative complica- tions were analysed. Total postoperative catheter time, total post-operative hospital stay, haemo- globin loss were also recorded in the two groups. RESULTS: Comparative data on IPSS symptom score, IIEF-5, Qol, PSA, peak urinary flow rate and post-void residual urine volume were similar in the two groups but showed a significant improve- ment respect to baseline values. The postoperative haemoglobin levels, postoperative catheteri- zation time, hospital stay and 3-year overall surgical re-treatment-free rate were significantly better in the bipolar group. CONCLUSIONS: Bipolar TURP has a comparable outcome to standard monopolar TURP at short and medium term regard to subjective and objective outcome measurements. Its impact on blad- der outlet function is also similar to that of monopolar TURP. Improvement in IPSS, Qol index, IIEF-5, Qmax and post-void residual urine volume were comparable in both group denoting sim- ilar efficacy of the techniques.


Subject(s)
Endoscopy/methods , Prostate/surgery , Prostatic Hyperplasia/surgery , Transurethral Resection of Prostate/methods , Urinary Bladder Neck Obstruction/surgery , Aged , Blood Loss, Surgical , Follow-Up Studies , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Patient Satisfaction , Postoperative Complications/epidemiology , Prostatic Hyperplasia/complications , Prostatic Hyperplasia/physiopathology , Recurrence , Sodium Chloride , Therapeutic Irrigation , Transurethral Resection of Prostate/instrumentation , Treatment Outcome , Urinary Bladder Neck Obstruction/etiology , Urinary Bladder Neck Obstruction/physiopathology , Urinary Catheterization/statistics & numerical data , Urodynamics
4.
Arch Ital Urol Androl ; 84(3): 165-6, 2012 Sep.
Article in English | MEDLINE | ID: mdl-23210412

ABSTRACT

Angiomyolipomas (AML) are mesenchymal tumors of the kidney consisting of varying proportions of vascular, immature smooth muscle and mature fat cells. A rare case of testicular AML is described. A 53 year old male with a history of congenital motor defects, mental retardation, and hypertension, presented to the emergency room with sudden onset, severe left testicular pain. Scrotal sonography demonstrated an hypoechoic mass in the patient's left testicle. The patient was offered and underwent a trans-inguinal exploration of the left testicle which ended in a left inguinal orchiectomy. Pathologic examination of the mass revealed medium to large calibre thick-walled blood vessels with ectatic lumina, surround by sclerotic, fibrous smooth muscle bundles in a fatty milieu. Immunohistochemistry of the lesion demonstrated positive staining for smooth muscle actin (SMA+) and endothelial marker CD34. The lesion did not, however, stain positively for smooth muscle antigen S100 or melanocytic antigen HMB-45.


Subject(s)
Angiomyolipoma , Neoplasms, Multiple Primary , Spermatic Cord , Testicular Neoplasms , Angiomyolipoma/diagnosis , Genital Neoplasms, Male/diagnosis , Humans , Male , Middle Aged , Neoplasms, Multiple Primary/diagnosis , Testicular Neoplasms/diagnosis
5.
Arch Ital Urol Androl ; 84(2): 94-8, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22908779

ABSTRACT

INTRODUCTION: Chronic benign prostate diseases are very common and certainly feature significantly in urological practice.The treatment of chronic benign prostate diseases is a common problem in clinical practice: few studies have been conducted in routine clinical practice to evaluate the efficacy of the treatments for this clinical condition. The objective of this study was to evaluate the efficacy of an extract of Serenoa repens (Permixon) in the treatment of lower urinary tract symptoms (LUTS) in patients with chronic benign prostate diseases with associated inflammation, also taking into consideration the influence of treatment on sexual function and, therefore, on patients' quality of life. MATERIALS AND METHODS: All the 591 eligible subjects were evaluated on entering the study; after a screening visit, including medical history, physical examination, physical examination and digital rectal examination (DRE) and laboratory tests, the patients underwent uroflowmetry. The subjects under investigation were also asked to complete the IPSS, NIH-CPSI and IIEF-5 questionnaires, for the purpose of evaluating urinary symptoms and erectile function in relation to sexual activity in the previous 6 months. RESULTS: The analysis of the uroflowmetry results showed that treatment with extract of Serenoa repens distinctly improves bladder voiding and lower urinary tract symptoms, as highlighted also by the improvement in the scores for the IPSS and NIH-CPSI questionnaires which serve as a basis for evaluating the urinary symptoms of patients with prostatic hyperplasia and chronic prostatitis respectively. The results also suggest that using an extract of Serenoa repens for 6 months in patients with chronic benign prostate diseases gives rise to an improvement in erectile function, as demonstrated by the increase in the scores for the IIEF-5 questionnaire after 6 months of treatment. CONCLUSIONS: The results of this study demonstrate how treatment for 6 months with an extract of Serenoa repens in routine clinical practice gives rise to a statistically significant improvement in Qmax values and in the IPSS, NHI-CPSI and IIEF-5 questionnaire scores, resulting not only in an improvement in urinary symptoms but also in an overall improvement in patients' quality of life.


Subject(s)
Phytotherapy , Plant Extracts/therapeutic use , Prostatic Hyperplasia/drug therapy , Prostatitis/drug therapy , Serenoa , Adult , Aged , Humans , Male , Middle Aged , Prostatic Hyperplasia/complications , Prostatitis/complications
6.
Arch Ital Urol Androl ; 83(3): 154-9, 2011 Sep.
Article in English | MEDLINE | ID: mdl-22184840

ABSTRACT

OBJECTIVE: Aim of this study was to evaluate if saturation biopsy (SB) technique increases the cancer detection rate in patients with PSA < 10 ng/ml, after a first negative biopsy. MATERIAL AND METHODS: From January 2004 to January 2006, 780 patients underwent prostate ultrasound guided transrectal (UGT) core biopsy: 186 (23.8%) presented prostate cancer (PCa) while 594 pts (76.2%), were disease free. For 1 year all the patients with no evidence of cancer were observed according to a follow-up schedule including PSA every 3 months and DRE every 6 months. During this period 140 patients showed an increase of PSA (< 10 ng/ml) or a low PSA free/total. This group underwent a second prostate UGT core biopsy with SB technique. In all the patients we evaluated PCa detection rates (DR) according to the PSA range. We also checked peri/post-operative complication rate (total post-operative hospitalization time, haemoglobin loss, catheterisation rate, pain rate, QOL). RESULTS: Of the 140 patients 50 (35.7%) had PCa showing a Gleason score (GS) of 4 or 5 in 26%, 6 or 7 in 75% and 8 to 10 in 9% respectively. Sectors apical biopsies carried out in the anterior horn of peripheral zone tissue presented over 70% (35 patients) of cancer detection rate. Rectal bleeding was the major common complication. Cancer was clinically significant in 47 patients (94%) but 34 (68%) presented an organ confined disease after radical surgery. CONCLUSIONS: SB technique increases of 35.7% the cancer detection rate (DR) in patients with PSA < 10 ng/ml, after a first negative biopsy, showing a higher positivity (70% PCaDR) if the SB included the anterior horn of peripheral zone tissue. No significantly pain and side effects were observed.


Subject(s)
Adenocarcinoma/diagnosis , Biopsy , Prostate-Specific Antigen/blood , Prostatic Neoplasms/diagnosis , Adenocarcinoma/blood , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Biomarkers, Tumor/blood , Biopsy/methods , Biopsy, Needle , Equipment Design , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Grading , Predictive Value of Tests , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Retrospective Studies , Sensitivity and Specificity , Treatment Outcome , Ultrasonography, Interventional
7.
Arch Ital Urol Androl ; 83(2): 88-94, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21826881

ABSTRACT

OBJECTIVES: With the advent of medical management and minimally techniques for benign prostate hypeplasia (BPH), invasive surgical procedures such open prostatectomy (OPSU) have become less common, although selected patients may still benefit from open prostatectomy. Aim of this study was to evaluate efficacy and safety of Bipolar TURP (Gyrus electro surgical system) versus standard open prostatectomy in patients with lower urinary tract symptoms (LUTS) due to bladder outlet obstruction (BOO) with markedly enlarged glands refractory to medical therapy. METHODS: From January 2003 to January 2004, 140 patients affected by mild-severe LUTS, secondary to BOO from BPH, refractory to medical therapy, with markedly enlarged glands, were randomized in two groups (1:1), and subjected to open prostatectomy (OPSU) carried out with traditional method (Bracci Thechnique) versus transurethral resection of the prostate (TURP) utilizing the bipolar methodology. Preoperative work-up included IPSS, IIEF-5 and Qol questionnaires. All patients were submitted to uroflowmetry, transrectal ultrasound (TRUS), measurament of postvoidal residual urine and PSA determination. IPSS, IIEF-5 and Qol, uroflowmetry, TRUS, measurement of post-voidal residual urine, PSA determination and number of reoperations were evaluated at 1, 3, 6, 12, 18, 24, 30 and 36 months. Operative time, resected tissue weight and perioperative complications were also registered. Total post-operative catheter time, total postoperative hospital stay, haemoglobin loss were recorded in the 2 groups. RESULTS: Comparative data on IPSS symptom score, IIEF-5 and Qol, PSA, peak urinary flow rates and post-void residual urine volume in the 2 groups were similar but showed a significative improvement with respect to baseline value. Postoperative haemoglobin levels, postoperative catheterization, hospital stay and 3-yr overall surgical re-treatment-free rate were significantly better in the Bipolar group. CONCLUSIONS: In the treatment of LUTS due to bladder outlet obstruction (BOO) with markedly enlarged glands refractory to medical therapy, Bipolar TURP has a comparable outcome to open prostatectomy at short and medium term according to both subjective and objective outcome measures.


Subject(s)
Electrosurgery , Prostatectomy/methods , Prostatic Hyperplasia/surgery , Prostatism/surgery , Urinary Bladder Neck Obstruction/surgery , Aged , Humans , Male , Organ Size , Prostate/pathology , Prostatic Hyperplasia/complications , Prostatic Hyperplasia/pathology , Prostatism/etiology , Transurethral Resection of Prostate/methods , Urinary Bladder Neck Obstruction/etiology
8.
Arch Ital Urol Androl ; 82(3): 172-4, 2010 Sep.
Article in English | MEDLINE | ID: mdl-21121437

ABSTRACT

INTRODUCTION: It is advisable to submit a patient with isolated HGPIN to re-biopsy every 3-6 months, performing an increasing number of samples in order to increase the detection rate. The aim of this study is to evaluate if the use of saturation needle biopsy technique may increase this rate. MATERIALS AND METHODS: From January 2004 to June 2006, 780 patients with hypoecogenic nodule at TRUS and/or PSA values between 2.5 and 10 ng/ml, underwent TRUS 10-core prostate needle biopsy, performed by the same operator Isolated HGPIN was detected in 26 cases (3.3%). Within a year all these patients underwent saturation needle re-biopsy. This procedure consisted of 24 samples obtained using a tru-cut needle 18 G under soft anesthesia by a major opiate. All the patients received a single dose of Levofloxacin per os before the biopsy and for the following 2 days. RESULTS: Prostate cancer was found in 8 (33.3%) of the 24 eligible patients: 40% showed a Gleason Score 6 and 60% > 7. Concerning PSA, we observed 35% of neoplasms for values between 2.5 and 3.9 ng/ml and the remaining 65.0% for values between 4.0 and 9.9 ng/ml. CONCLUSIONS: The use of saturation needle biopsy allowed to detect 30.8% of prostatic cancer performing the first re-biopsy within a year. This result does not differ from others obtained with 8-10 cores techniques, therefore the indication of the 24-cores procedure should be limited to carefully selected patients with a high risk of developing cancer after that other techniques had not been successful.


Subject(s)
Biopsy, Needle/methods , Prostatic Intraepithelial Neoplasia/pathology , Prostatic Neoplasms/pathology , Adult , Aged , Humans , Male , Middle Aged , Risk Assessment
9.
Arch Gen Psychiatry ; 67(3): 258-67, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20194826

ABSTRACT

CONTEXT: Brain-derived neurotrophic factor (BDNF) plays a pivotal role in the pathophysiology of suicidal behavior and BDNF levels are decreased in the brain and plasma of suicide subjects. So far, the mechanisms leading to downregulation of BDNF expression are poorly understood. OBJECTIVES: To test the hypothesis that alterations of DNA methylation could be involved in the dysregulation of BDNF gene expression in the brain of suicide subjects. DESIGN: Three independent quantitative methylation techniques were performed on postmortem samples of brain tissue. BDNF messenger RNA levels were determined by quantitative real-time polymerase chain reaction. SETTING: Academic medical center. PATIENTS OR OTHER PARTICIPANTS: Forty-four suicide completers and 33 nonsuicide control subjects of white ethnicity. MAIN OUTCOME MEASURES: The DNA methylation degree at BDNF promoter IV and the genome-wide DNA methylation levels in the brain's Wernicke area. RESULTS: Postmortem brain samples from suicide subjects showed a statistically significant increase of DNA methylation at specific CpG sites in BDNF promoter/exon IV compared with nonsuicide control subjects (P < .001). Most of the CpG sites lying in the -300/+500 region, on both strands, had low or no methylation, with the exception of a few sites located near the transcriptional start site that had differential methylation, while genome-wide methylation levels were comparable among the subjects. The mean methylation degree at the 4 CpG sites analyzed by pyrosequencing was always less than 12.9% in the 33 nonsuicide control subjects, while in 13 of 44 suicide victims (30%), the mean methylation degree ranged between 13.1% and 34.2%. Higher methylation degree corresponded to lower BDNF messenger RNA levels. CONCLUSIONS: BDNF promoter/exon IV is frequently hypermethylated in the Wernicke area of the postmortem brain of suicide subjects irrespective of genome-wide methylation levels, indicating that a gene-specific increase in DNA methylation could cause or contribute to the downregulation of BDNF expression in suicide subjects. The reported data reveal a novel link between epigenetic alteration in the brain and suicidal behavior.


Subject(s)
Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , DNA Methylation/genetics , Promoter Regions, Genetic/genetics , Suicide/statistics & numerical data , Temporal Lobe/metabolism , Adolescent , Adult , Aged , Cloning, Molecular/methods , Down-Regulation/genetics , Female , Gene Expression Profiling , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , Promoter Regions, Genetic/physiology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Suicide/psychology , White People/genetics
10.
BMC Infect Dis ; 9: 86, 2009 Jun 07.
Article in English | MEDLINE | ID: mdl-19500412

ABSTRACT

BACKGROUND: In Italy, HBV vaccination is recommended and offered free of charge through the National Health Service to selected population groups -- e.g., family members of an HBsAg carrier, healthcare workers, newborns and those who were 12-years old in 1991. However, a significant proportion of cases of acute hepatitis B still occur in Italy among persons who should have been vaccinated. We analysed HBV sero-prevalence data of two vaccination target populations (people born after 1980 and household contacts of an HBV carrier) living in a southern Italian area in order to evaluate HBV vaccine coverage and its possible determinants. METHODS: Between 2003 and 2006, we carried out a cross-sectional, population-based, sero-epidemiological survey on HBV infection on 4496 randomly selected individuals (aged 20 years or more) from the general population of the province of Naples. Sera were tested for antibodies to hepatitis B core antigen (anti-HBc) and to hepatitis B surface antigen (anti-HBsAg) by commercial immunoassays. Prevalence of past or current HBV infection and of HBV vaccination-induced immunity was calculated in two vaccination target populations. To analyze the association of epidemiological and socioeconomic characteristics with HBV vaccination of household contacts, we calculated crude and multiple logistic regression (MLR) odds ratio (OR). RESULTS: Prevalence of HBV vaccine-induced immunity (anti-HBs alone) was much lower among household contacts (25%) than among those who had been targeted for universal adolescent vaccination (81.6%). Male sex, older age, unemployment and lower education levels were associated to lower immunization rates. CONCLUSION: Understanding the different uptake of hepatitis B vaccination in these populations may provide useful information for optimizing vaccination campaigns in other contexts. Our data clearly demonstrated the need of improving the uptake of vaccination for household contacts of HBV carriers.


Subject(s)
Hepatitis B Vaccines/immunology , Hepatitis B/epidemiology , Adult , Demography , Female , Health Policy , Hepatitis B/immunology , Hepatitis B/prevention & control , Hepatitis B Antibodies/blood , Hepatitis B Core Antigens/immunology , Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines/economics , Hepatitis B virus/immunology , Humans , Italy/epidemiology , Male , Seroepidemiologic Studies , Socioeconomic Factors
11.
Eur J Cancer ; 44(6): 847-53, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18313290

ABSTRACT

Southern Italy shows the highest rates of liver cancer for Europe, mainly related to infection with hepatitis viruses. We thus described incidence rates of liver cancer and investigated prevalence and determinants of HCV and HBV infections in 4496 individuals randomly selected from the general population of the province of Naples. 7.5% was infected with HCV and 27.6% with HBV (2.2% was HBsAg-positive). Prevalence of both infections increased with age, 23.2% of those aged 65 years or older was HCV-positive and 47.9% were HBV-positive. Intravenous drug use (odds ratio (OR)=16.4 for anti-HCV and 4.7 for anti-HBc), history of blood transfusions (OR=2.8 and 1.5, respectively) and surgery, and household contacts with infected people (OR=2.1 and 1.6, respectively) increased risks for both infections. Sexual intercourse with HCV-positive individuals conveyed a 3-fold higher risk of HCV infection. This study quantified the spread of HCV and HBV in the population of southern Italy heavily affected by liver cancer.


Subject(s)
Hepatitis B, Chronic/epidemiology , Hepatitis C, Chronic/epidemiology , Liver Neoplasms/epidemiology , Adult , Age Distribution , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Incidence , Italy/epidemiology , Male , Middle Aged , Sex Distribution
12.
Mol Med ; 8(9): 536-45, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12456992

ABSTRACT

BACKGROUND: In vitro studies have demonstrated that interleukin (IL)-1beta decreases insulin and DNA contents in pancreatic islet beta cells, causing structural damage, that it is toxic to cultured human islet beta cells and that it is able to induce apoptosis in these cells. MATERIALS AND METHODS: Isolated rat islets of Langerhans were exposed in vitro to interleukin (IL)-1beta and either the imidazoline compound RX871024 (RX) or/and M40403, an Mn-containing superoxide dismutase mimetic (MnSODm). RESULTS: Insulin secretion, on days 1, 2 and 3 after challenge with 3 ng/ml of IL-1beta, was almost abolished and this was accompanied by an early increase in MnSOD activity. By days 2 and 3, SOD activities were lower than those of untreated controls and NO significantly increased by day 2. Moreover, IL-1beta induced a significant increase in MnSOD transcripts, while iNOS mRNA appeared by days 2 and 3 when MnSOD mRNA was absent. RX blocked all toxic effects of IL-1beta by maintaining insulin secretion and islet beta cell phenotype, including the inhibition of nonspecific proteins and of iNOS induction. In contrast, the MnSODm, failed to counteract iNOS induction as well as the reduced insulin secretion. CONCLUSIONS: In summary, our findings stress that IL-1beta-induced suppression of insulin secretion may be related to iNOS induction in beta cells and that RX can reverse this effect, by maintaining insulin secretion. Oppositely, the MnSODm is not able to restore IL-1beta-suppressed insulin secretion. Hence, imidazoline compounds may protect beta cells against damage caused by IL-1beta-induced free oxygen and nitrogen radicals.


Subject(s)
Imidazoles/pharmacology , Indoles/pharmacology , Interleukin-1/toxicity , Islets of Langerhans/drug effects , Animals , Insulin/metabolism , Insulin Secretion , Interleukin-1/antagonists & inhibitors , Islets of Langerhans/metabolism , Manganese , Nitric Oxide/metabolism , Nitric Oxide Synthase/biosynthesis , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase Type II , Organometallic Compounds/pharmacology , RNA, Messenger/metabolism , Rats , Rats, Wistar , Superoxide Dismutase/biosynthesis , Superoxide Dismutase/drug effects , Superoxide Dismutase/genetics
13.
J Cell Biochem ; 86(4): 651-64, 2002.
Article in English | MEDLINE | ID: mdl-12210732

ABSTRACT

In this study, we show that intra- and peri-islet microvascular areas undergo different changes during the islet inflammation in the nonobese diabetes-prone female mice. Actually, although the islet vascular area (IVA) considerably decreases while the infiltration progresses, at 15 weeks of age, the peri-islet vascular bed is unexpectedly and significantly increased. On the contrary, the intra-IVA is significantly decreased, due to vessel dilation. Later, by 20-25 weeks of age, a decrease of both IVA occur, due to a significant islet beta cell loss. Moreover, a dramatic fall of natural free radical scavenger values, which, in turn, exert an influence upon vessels, is observed. These effects are completely counteracted by the administration of IL-4, a Th2 protective cytokine; IL-10, another putative Th2 cytokine, exerts direct effects upon endothelial cell (EC) function, as shown by the increase of endothelial nitric oxide synthase (eNOS) mRNA transcripts and by the release of endothelial NO which, in turn, exert vasodilatory effects; moreover, this cytokine significantly upregulates adhesion molecules on endothelia. On the other hand, IL-1beta, a Th1 proinflammatory cytokine, dramatically increases nitrite and nitrate levels, as well as inducible nitric oxide synthase (iNOS) transcripts and also upregulates islet ICAM-1 expression as well as circulating ICAM-1 levels. Taken together, our findings clearly show that cytokines and islet endothelia are directly involved in the pathophysiology of the disease. Their reciprocal influence gives new insight to understand the role of microvasculature during islet beta cell attack.


Subject(s)
Cytokines/physiology , Islets of Langerhans/blood supply , Th1 Cells/metabolism , Th2 Cells/metabolism , Animals , Blood Glucose/analysis , Cell Culture Techniques , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Female , Intercellular Adhesion Molecule-1/metabolism , Interleukins/pharmacology , Islets of Langerhans/cytology , Islets of Langerhans/metabolism , Mice , Mice, Inbred NOD , Microcirculation/physiology , Microscopy/methods , Nitrates/analysis , Nitric Oxide/metabolism , Nitrites/analysis , Oxidoreductases/metabolism , RNA/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Time Factors
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