Blockade of CCR4 diminishes hypersensitivity and enhances opioid analgesia : evidence from a mouse model of diabetic neuropathy

Chemokine signaling has been implicated in the pathogenesis of diabetic neuropathy; however, the role of chemokine CC motif receptor 4 (CCR4) remains unknown. The goal was to examine the function of CCR4 in hypersensitivity development and opioid effectiveness in diabetic neuropathy. Streptozotocin (STZ; 200 mg/kg, intraperitoneally administered)-induced mouse model of diabetic neuropathy were used. An analysis of the mRNA/protein expression of CCR4 and its ligands was performed by qRT-PCR, microarray and/or Western blot methods. C021 (CCR4 antagonist), morphine and buprenorphine were injected intrathecally or intraperitoneally, and pain-related behavior was evaluated by the von Frey, cold plate and rotarod tests. We observed that on day 7 after STZ administration, the blood glucose level was increased, and as a consequence, hypersensitivity to tactile and thermal stimuli developed. In addition, we observed an increase in the mRNA level of CCL2 but not CCL17/CCL22. The microarray technique showed that the CCL2 protein level was also upregulated. In naive mice, the pronociceptive effect of intrathecally injected CCL2 was blocked by C021, suggesting that this chemokine acts through CCR4. Importantly, our results provide the first evidence that in a mouse model of diabetic neuropathy, single intrathecal and intraperitoneal injections of C021 diminished neuropathic pain-related behavior in a dose-dependent manner and improved motor functions. Moreover, both single intrathecal and intraperitoneal injections of C021 enhanced morphine and buprenorphine effectiveness. These results reveal that pharmacological modulation of CCR4 may be a good potential therapeutic target for the treatment of diabetic neuropathy and may enhance the effectiveness of opioids

Changes in inflammatory biomarkers after successful lifestyle intervention in obese children

Background: Obesity has been associated with low-grade systemic inflammation, potentially leading to insulin resistance, type 2 diabetes, dyslipidemia, and cardiovascular diseases. Even moderate weight loss through dietary changes and physical exercise is effective in preventing and managing obesity-associated disorders. The aim of this study was to determine the effect of weight loss in response to a lifestyle modification on the serum levels of inflammatory markers in obese children and adolescents. Material and methods: Fifty obese subjects completed a six-month programme consisting of combined hypocaloric diet and moderate physical activity. High-sensitive C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen (FB), white blood count (WBC), glucose, insulin, insulin resistance index (HOMA IR), glycosylated haemoglobin (HbA1c), lipids as well as systolic (SBP) and diastolic blood pressure (DBP) were measured before and after intervention. Results: Patients had a 5.3 ± 3.4 kg average weight loss, with significant decreases of SDS-BMI, percentage of body fat, SDS-waist, SBP and DBP, HOMA-IR, HbA1c and reductions in serum IL-6, CRP, WBC, FB. In the multivariable linear models, changes in percentage of body fat and HOMA-IR were positively associated with favourable changes in inflammatory parameters. Conclusion: This study demonstrates that weight reduction after successful lifestyle intervention results in improvements of blood inflammatory markers in obese children and adolescents. (Pol J Endocrinol 2011; 62 (6): 499–505)Wstęp: Otyłość wiąże się z obecnością niewielkiego stopnia stanu zapalnego, potencjalnie prowadzącego do insulinooporności, cukrzycy typu 2, dyslipidemii i chorób sercowo-naczyniowych. Nawet umiarkowane obniżenie masy ciała dzięki zmianie diety i zwiększonej aktywności fizycznej zapobiega występowaniu zaburzeń związanych z otyłością. Celem pracy była ocena wpływu obniżenia masy ciała (w wyniku modyfikacji stylu życia) na stężenie wskaźników stanu zapalnego w surowicy otyłych dzieci i młodzieży. Materiał i metody: W 6-miesięcznym programie polegającym na stosowaniu ubogokalorycznej diety i umiarkowanej aktywności fizycznej uczestniczyło 50 otyłych pacjentów. W warunkach podstawowych i po 6 miesiącach oznaczano: białko C-reaktywne (CRP), interleukinę 6 (IL-6), fibrynogen (FB), leukocyty (WBC), glukozę, insulinę, wskaźnik insulinooporności (HOMA-IR), hemoglobinę glikozylową (HbA1c), lipidy, ciśnienie tętnicze krwi skurczowe (SBD) i rozkurczowe (DBD). Wyniki: Średni spadek masy ciała u pacjentów wynosił 5,3 ± 3,4 kg, ze znaczącą redukcją wartości SDS-BMI, procentowej zawartości tłuszczu, SDS-obwodu pasa, SBP i DBP, HOMA-IR, HbA1c oraz obniżeniem stężeń IL-6, CRP, WBC, FB w surowicy. W wieloczynnikowej analizie regresji zmiany w procentowej zawartości tłuszczu i HOMA-IR były pozytywnie skorelowane z podobnymi zmianami wskaźników stanu zapalnego. Wnioski: Redukcja masy ciała w efekcie zmiany stylu życia wpływa na poprawę wskaźników stanu zapalnego u otyłych dzieci i młodzieży. (Endokrynol Pol 2011; 62 (6): 499–505

Stężenie 25-hydroksywitaminy D (25-OH-D) u otyłych nastolatków

Background: There is increasing evidence that vitamin D deficiency is common and has been associated with several non-bone related outcomes, including insulin resistance, type 2 diabetes and cardiovascular disease. The influences of gender, puberty, and adiposity on serum hydroxyvitamin D (25-OH-D) levels and the relationship between 25-OH-D and insulin resistance in obese children were studied. Material and methods: Age, gender, pubertal stage, weight status (standard deviation score of body mass index: BMI-SDS, percentage body fat, waist circumference), 25-OH-D levels, and insulin resistance index calculated by homeostasis model assessment (HOMA-IR) were evaluated in 64 obese adolescents. Multivariable linear regression was used to determine factors associated with decreased serum 25-OH-D levels and to study the relationship between 25-OH-D and HOMA-IR. Results: Median serum 25-OH-D level was 10.1 ng/mL (25.2 nmol/L). 14% of patients were vitamin D-sufficient (25-OH-D ≥ 20 ng/mL), 36% had intermediate values (11–19 ng/mL), and 50% were deficient (25-OH-D ≤ 10 ng/mL). In the multivariable model, older age, puberty, higher value of percentage of body fat, and the presence of acanthosis nigricans (AN) were all negatively associated with 25-OH-D. Lower 25-OH-D levels were also associated with higher blood glucose, insulin and HOMA-IR after adjustment for puberty and SDS-BMI. Summer positively correlated with 25-OH-D level. Conclusion: Our study confirms that obesity is a risk factor for vitamin D deficiency. Hypovitaminosis D, common in obese adolescents at risk for type 2 diabetes (older age, puberty, acanthosis nigricans) is associated with worse insulin resistance. (Pol J Endocrinol 2011; 62 (6): 506–511)Wstęp: Niedobór witaminy D jest zjawiskiem coraz bardziej powszechnym i związanym nie tylko z zaburzeniami metabolizmu kostnego, ale też z insulinoopornością, cukrzycą typu 2 i chorobami sercowo-naczyniowymi. Celem pracy było badanie wpływu płci, stadium pokwitania i otyłości na stężenie 25-OH-D w surowicy oraz zależności między witaminą D a insulinoopornością u otyłych dzieci. Materiał i metody: U 64 otyłych nastolatków oceniano wiek, płeć, stadium pokwitania, stopień otyłości i wskaźnik insulinooporności (HOMA-IR). Do określenia czynników wpływających na obniżenie stężenia 25-OH-D w surowicy oraz do oceny zależności między 25-OH-D a HOMA-IR wykorzystano wielowymiarową analizę regresji. Wyniki: Mediana stężenia 25-OH-D w surowicy wynosiła 10,1 ng/mL (25,2 mmol/L). Tylko u 14% pacjentów stężenie 25-OH-D w surowicy było wystarczające (≥ 20 ng/mL), u 36% wartości te wynosiły 11–19 ng/mL, u 50% stwierdzono znaczny niedobór 25-OH-D (≤ 10 ng/mL). W wielowymiarowej analizie regresji starszy wiek, bardziej zaawansowane stadium pokwitania, większy odsetek zawartości tłuszczu i obecność rogowacenia ciemnego korelowały negatywnie ze stężeniem witaminy D. Niższe stężenia 25-OH-D wiązały się z wyższym stężeniem glukozy, insuliny i HOMA-IR przy uwzględnieniu stadium pokwitania i SDS-BMI. Okres letni pozytywnie korelował ze stężeniem 25-OH-D. Wnioski: Otyłość jest czynnikiem ryzyka niedoboru witaminy D. Niedobór witaminy D powszechny u otyłych nastolatków zagrożonych cukrzycą typu 2 wiąże się z większą insulinoopornością. (Endokrynol Pol 2011; 62 (6): 506–511

Quality of life versus semen parameters

Abstract Introduction: Psychological factors are believed to play an important role in infertility and its treatment. Psychological problems may be considered to be risk factors and the cause of reduced infertility, as well as contribute to an unsuccessful outcome of infertility treatment. Objectives: The aim of the study was to investigate the correlation between semen parameters and quality of life in male patients with fertility problems. Material and methods: 70 patients with infertility treated in Andrology Clinic were divided into two groups according to semen parameters: bad and good quality of semen. The quality of life has been with the help of Campbell questionnaires. Results: Significantly lower questionnaire score in bad quality of semen group has been observed, in comparison with normozoospermic men. High correlation between concentration, motility and morphology in comparison with the quality of life has been observed in the studied group of patients. Conclusion: The quality of life is directly associated with semen parameters such as concentration, motility and morphology of sperm

Adenosine deaminase activity in tuberculous and malignant pleural effusions

Measurement of pleural adenosine deaminase activity (ADA) is a useful diagnostic tool for tuberculous pleurisy, but false-positive findings from non-tuberculous effusions have been reported. In order to improve diagnostic value of ADA it is recommended to estimate activity of both ADA1 and ADA2 izoenzymes or 2'-deoxyadenosine/adenosine activity ratio. In order to evaluate ADA as a diagnostic parameter total ADA, with adenosine as a substrate, and 2'-deoxyadenosine/adenosine activity ratio were measured in tuberculous and malignant pleural effusions. Altogether, 26 pleural exudates (11 tuberculous and 15 malignant) were selected. ADA either with adenosine or 2'-deoxyadenosine was determined by colorimetric method of Giusti. Each pleural fluid sample was diluted prior to the assay(1:8)to avoid enzyme inhibition which was observed in nondiluted pleural effusions. The ADA level reached the diagnostic cut-off set for tuberculous effusions (40 U/L) in every 11 tuberculous exudates with the mean value of 85,3±47,1U/L; in 9 of these the 2'-deoxyadenosine/adenosine ratio was less than 0,45. In the malignant group of patients, no one ADA level exceed 40 U/L, being estimated at 10,6±7,7 U/L (

Breast carcinoma and anaplastic gastric carcinoma with pleural metastases in patient after mastectomy 30 years ago

We describe a case of two simultaneous malignancies - anaplastic gastric carcinoma with pleural metastases and left breast carcinoma. These malignancies were recognized in 78-year old woman after right mastectomy performed 30 years ago. Additionaly, during diagnostic procedures rectal polypus found during colonoscopy occurred to be adenoma tubulovillosum. Her parents died from malignancies - mother from gastric cancer and father from pulmonary carcinoma. One should remember that there is always possibility of simultaneous development of more than one primary malignancies in one patient and neoplastic disease is an important cancer risk factor. This observation confirms the important role of genetic factors in the pathogenesis of malignant diseases

Course of fatigue among patients previously hospitalised due to COVID-19

Introduction. Discrepancies exist regarding the clinical course and prognostic factors for post-COVID fatigue. Therefore, our aim was to assess the timely course of fatigue and its possible predictors in patients previously hospitalised due to SARS-CoV-2 infection. Material and methods. Patients and employees of the University Hospital in Krakow were assessed with the use of a validated neuropsychological questionnaire. Included were participants aged 18 or more, previously hospitalised due to COVID-19, who completed questionnaires only once > 3 months after the onset of infection. Individuals were retrospectively asked about the presence of eight symptoms of chronic fatigue syndrome at four timepoints: before COVID-19, within 0–4 weeks, 4–12 weeks, and > 12 weeks post-infection. Results. We enrolled 204 patients [40.2% women, median age 58 (46–66) years] evaluated after a median of 187 (156–220) days from the first positive nasal swab test for SARS-CoV-2. The most common comorbidities were hypertension (44.61%), obesity (36.27%), smoking (28.43%), and hypercholesterolemia (21.08%); none of the patients required mechanical ventilation during hospitalisation. Before COVID-19, 43.62% of patients reported at least one symptom of chronic fatigue. Within 4, 4–12, and > 12 weeks after COVID-19, the prevalence of chronic fatigue was 76.96%, 75.49%, and 66.17%, respectively (all p < 0.001). The frequency of chronic fatigue symptoms decreased within > 12 weeks following the onset of infection but did not return to baseline values, except for self-reported lymph node enlargement. In a multivariable linear regression model, the number of fatigue symptoms was predicted by female sex [β 0.25 (0.12; 0.39), p < 0.001 and 0.26 (0.13; 0.39), p < 0.001 for weeks 0–12 and > 12, respectively], and age [for < 4 weeks, β –0.12 (–0.28; –0.01), p = 0.029]. Conclusions. Most patients previously hospitalised due to COVID-19 suffer from fatigue > 12 weeks after infection onset. The presence of fatigue is predicted by female sex and – only for the acute phase — age

Mechanical thrombectomy for acute ischaemic stroke during therapeutic anticoagulation: long-term outcomes

Aim of study. Mechanical thrombectomy (MT) is one of the aetiological treatment options recommended for anticoagulated patients with acute ischaemic stroke (AIS). We analysed its long-term outcomes using the modified Rankin Score (mRS) or mortality on day 90.Clinical rationale for the study. Data describing the anticoagulant efficacy and safety of MT in patients with AIS is limited.Materials and methods. This study included 291 patients with AIS (49% women, mean [SD] age 66 [15] years) who underwent MT in the Comprehensive Stroke Centre in Krakow, Poland. Data describing demographics, stroke risk factors, NIHSS on admission, postprocedural thrombolysis in cerebral infarction score, 24-hour postprocedural haemorrhagic transformation (ECASS-2) as seen on computed tomography, and time between stroke onset and groin puncture was collected. The outcome measure was the mRS on day 90 after stroke onset (a favourable outcome was defined as an mRS not exceeding 2 points; an unfavourable outcome was death).Results. Thirty-seven patients (13%) were on therapeutic anticoagulation during MT. Univariate analysis showed that anticoagulated patients were older and more likely to have been diagnosed with hypertension, ischaemic heart disease, or atrial fibrillation. The patient groups did not differ in terms of clot location, postprocedural thrombolysis in cerebral infarction score, haemorrhagic transformation on computed tomography, or mRS on day 90. Multivariate logistic regression analysis showed that younger age, male sex, no history of diabetes mellitus, lower NIHSS score on admission, shorter time between stroke onset and groin puncture, and better recanalisation were associated with favourable outcomes at day 90, and that therapeutic anticoagulation was not (OR, 1.00; 95%CI, 0.46-2.15; p = 0.99). Anticoagulation did not affect mortality at day 90 (OR, 1.28; 95%CI, 0.56-2.92; p = 0.55).Conclusion and clinical implications. In anticoagulated patients with AIS, MT does not affect long-term outcomes