The painful shoulder: Part II. Intrinsic disorders and impingement syndrome

Intrinsic disorders that can cause shoulder pain include arthritis, gout, pseudogout and osteonecrosis. In its mildest form, impingement syndrome may cause only minimal discomfort. At its worst, impingement syndrome may lead to rotator cuff tear. Bicipital tendinitis and rupture of the biceps tendon may also be associated with impingement. Early rehabilitative intervention is important. Physical therapy is directed toward restoring range of motion and muscle strength.     

Serotonergic modulation of rat pineal gland activity: in vivo evidence for a 5-Hydroxytryptamine(2C) receptor involvement

There are some suggestions that, in the pineal gland, serotonin acts not only as a precursor of melatonin but also plays a role in the modulation of the pineal biosynthetic activity. To corroborate this possible neuromodulatory role of 5-hydroxytryptamine (serotonin) (5-HT) on the pineal gland, the effects of two 5-HT(2) receptor agonists meta-chlorophenylpiperazine (m-CPP) and 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane were assessed in vivo on pineal N-acetyltransferase (NAT) activity and melatonin content in rats. m-CPP potentiated the enhancement of NAT activity and pineal melatonin content induced by isoproterenol administration during daytime, whereas it did not affect the diurnal basal biosynthetic activity of the gland. At night, m-CPP and 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane enhanced significantly the physiological increases in both pineal NAT activity and melatonin content. This enhancement was prevented by pretreatment with N-(1-methyl-5-indolyl)-N'-(3-pyridyl) urea hydrochloride, an antagonist with higher affinity for 5-HT(2B/C) than for 5-HT(2A) receptor, as well as by pretreatment with 8-[5-(2, 4-dimethoxy-5-(4-trifluoromethyl-phenylsulphonamido)-phenyl-5-o xopent hyl]-1,3,8-triazospiro[4,5]decane-2,4-dione, the most specific 5-HT(2C) receptor now available, but not by pretreatment with ketanserin, an antagonist with higher affinity for 5-HT(2A) than for 5-HT(2C) receptor. These results suggest that 5-HT(2C) receptors are likely involved in the mediation of the serotonergic modulation of pineal biosynthetic activity in rats.     

Biochemical and neurobehavioral profile of CHF2819, a novel, orally active acetylcholinesterase inhibitor for Alzheimer's disease

1,2,3,3a,8,8a-Hexahydro-1,3a,8-trimethylpyrrolo?2,3-b?ndol-5-ol 2-ethylphenylcarbamate N-oxide hydrochloride (3aS-cis) (CHF2819) is a novel acetylcholinesterase inhibitor that produces central cholinergic stimulation after oral administration in rats. In vivo studies show that CHF2819 (0.5, 1.5, and 4.5 mg/kg p.o.) significantly increases acetylcholine levels in young adult rat hippocampus in a dose-dependent manner. Moreover, aged animals, which show a significant decrease in basal acetylcholine levels with respect to young adult rats, also exhibit a marked increase in the hippocampal concentrations of this neurotransmitter after the administration of CHF2819. This compound (1.5 mg/kg p.o.) significantly attenuates scopolamine-induced amnesia in a passive avoidance task. Furthermore, CHF2819 induces a significant decrease in dopamine levels and a significant elevation of extracellular concentrations of 5-hydroxytryptamine, whereas it does not modify norepinephrine and gamma-aminobutyric acid levels in the hippocampus of young adult rats. Functional observational battery screening demonstrates that CHF2819 (1.5 and 4.5 mg/kg p.o.) does not affect activity, excitability, autonomic, neuromuscular, and sensorimotor domains, as well as physiological end points (body weight and temperature). However, this compound induces involuntary motor movements (ranging from mild tremors to myoclonic jerks) in a dose-dependent manner. These findings suggest that the anti-amnestic properties of CHF2819, together with its stimulatory effect on cholinergic and serotonergic functions, might have a therapeutic potential mainly for the symptomatic treatment of Alzheimer's disease patients in which the cognitive impairment is accompanied by a depressive syndrome.     

Anticipating Demand for Emergency Health Services due to Medication-related Adverse Events after Rapid Mass Prophylaxis Campaigns

Objectives: Mass prophylaxis against infectious disease outbreaks carries the risk of medication‐related adverse events (MRAEs). The authors sought to define the relationship between the rapidity of mass prophylaxis dispensing and the subsequent demand for emergency health services due to predictable MRAEs. Methods: The authors created a spreadsheet‐based computer model that calculates scenario‐specific predicted daily MRAE rates from user inputs by applying a probability distribution to the reported timing of MRAEs. A hypothetical two‐ to ten‐day prophylaxis campaign for one million people using recent data from both smallpox vaccination and anthrax chemoprophylaxis campaigns was modeled. Results: The length of a mass prophylaxis campaign plays an important role in determining the subsequent intensity in emergency services utilization due to real or suspected adverse events. A two‐day smallpox vaccination scenario would produce an estimated 32,000 medical encounters and 1,960 hospitalizations, peaking at 5,246 health care encounters six days after the start of the campaign; in contrast, a ten‐day campaign would lead to 41% lower peak surge, with a maximum of 3,106 encounters on the busiest day, ten days after initiation of the campaign. MRAEs with longer lead times, such as those associated with anthrax chemoprophylaxis, exhibit less variability based on campaign length (e.g., 124 out of an estimated 1,400 hospitalizations on day 20 after a two‐day campaign versus 103 on day 24 after a ten‐day campaign). Conclusions: The duration of a mass prophylaxis campaign may have a substantial impact on the timing and peak number of clinically significant MRAEs, with very short campaigns overwhelming existing emergency department (ED) capacity to treat real or suspected medication‐related injuries. While better reporting of both incidence and timing of MRAEs in future prophylaxis campaigns should improve the application of this model to community‐based emergency preparedness planning, these results highlight the need for coordination between public health and emergency medicine planning for infectious disease outbreaks to avoid preventable surges in ED utilization.     

Diagnostic value of changes in the Q wave induced by exertion

In order to evaluate the diagnostic value of exercise-induced Q wave changes and its relationship with the extent of coronary involvement and presence and location of a previous myocardial infarction, we examined the stress electrocardiograms of 188 consecutive patients with chest pain. Coronary arteriography shoved single vessel disease (SV) in 28 patients and multivessel disease (MV) in 130 patients; a previous myocardial infarction was present in 64 patients. The Q wave amplitude was measured as average of ten values in CM5 at rest and at peak exercise; a Delta-Q less than 0, i.e. reduction or no change of Q wave at peak exercise, was considered a positive response for coronary artery disease. The Delta-Q criterion shoved a significantly better sensitivity than ST depression, as a whole, but this improvement was nullified when patients with anterior myocardial infarction were excluded; as well specificity of Delta-Q although better than ST, did not allow a significant improvement for the diagnostic value of stress test. We also evaluated the diagnostic accuracy for multivessel coronary artery disease of both criteria positive was 78% whereas the negative predictive value of both criteria negative was 91%. We concluded that the exercise-induced Delta-Q less than 0 is a good indicator of coronary artery disease, although not superior to ST depression; the negativity of both criteria seems to be highly reliable for the exclusion of multivessel coronary artery disease.     

Cytomegalovirus Infection After Liver Transplantation: Prophylaxis and Preemptive Treatment—A Single-Center Experience

Background

Cytomegalovirus (CMV) infection represents one of the most frequent opportunistic infections following solid-organ transplantation. The incidence and severity of CMV infection depend on the immunosuppressive regimen, the CMV serostatus of donor and recipient, and the type of transplant.

Methods

We evaluated CMV infection rates during the last 2 years in our center: March 2007 to March 2009. We enrolled 55 patients—13 females and 42 males—who underwent liver transplantation (OLT) due to hepatitis C virus (HCV) cirrhosis (n = 9), hepatitis B virus (HBV) cirrhosis (n = 5) HCC both on HCV and HBV cirrhosis (n = 37), or autoimmune disease (n = 4). Fifty percent of the patients received tacrolimus (TRL) and the others cyclosporine (CsA), both dosed according to weight. All patients received oral acyclovir (400 mg/td or less, adapted to renal function) as herpes simplex prophylaxis for 6 months. CMV prophylaxis prescribed CMV- hyperimmunoglobulin on postoperative days 1 and 7. CMV infection was monitored using polymerase chain reaction (PCR <1000 IU/mL) according to the following schedule: every week for the first month, every 2 weeks from month 2 to 3 and monthly from month 4 to 6. Patients were treated when three positive PCR results not affected by immunosuppressive dose reduction or when the PCR showed DNA greater than three times the limit of detection. CMV treatment stipulated valgancyclovir (900 mg twice daily) until three consecutive PCRs were negative or for 3 months dosed according to renal function. PCR was measured every 2 weeks during treatment.

Results

Among the patients who were all D⁺/R⁺ (CMV-Immunoglobulin G [IgG]⁺/IgG⁺). 10 required treatment (18%) within 3 months from OLT. There subjects were prescribed TRL (n = 4) or CsA (n = 6). No renal impairment was observed among treated patients. Of those having the infection, one died due to other causes—sepsis from candida at 5 months after OLT.

Conclusion

CMV-hyperimmunoglobulin on postoperative days 1 and 7 did not confer protection for CMV among OLT patients. Preemptive treatment with intravenous gancyclovir plus valgancyclovir per os seemed to be useful and safe in infected patients requiring treatment.     

Characterization and evaluation of chitosan nanoparticles for dopamine brain delivery

The aim of this study was to characterize nanoparticles (NPs) composed of chitosan (CS) and evaluate their potential for brain delivery of the neurotransmitter Dopamine (DA). For this purpose, CS based NPs were incubated with DA at two different concentrations giving rise to nanocarriers denoted as DA/CSNPs (1) and DA/CSNPs (5), respectively. X-ray Photoelectron Spectroscopy (XPS) analysis confirmed that DA was adsorbed onto the external surface of such NPs. The cytotoxic effect of the CSNPs and DA/CSNPs was assessed using the MTT test and it was found that the nanovectors are less cytotoxic than the neurotransmitter DA after 3 h of incubation time. Transport studies across MDCKII-MDR1 cell line showed that DA/CSNPs (5) give rise to a significant transport enhancing effect compared with the control and greater than the corresponding DA/CSNPs (1). Measurement of reactive oxygen species (ROS) suggested a low DA/CSNPs neurotoxicity after 3 h. In vivo brain microdialysis experiments in rat showed that intraperitoneal acute administration of DA/CSNPs (5) (6-12 mg/kg) induced a dose-dependent increase in striatal DA output. Thus, these CS nanoparticles represent an interesting technological platform for DA brain delivery and, hence, may be useful for Parkinson's disease treatment.     

Extraction, characterization and in vivo neuromodulatory activity of phytosterols from microalga Dunaliella tertiolecta

In recent years, a great deal of research has been devoted to identify new natural sources of phytosterols and to improve methods for their recovery and purification. In this regard, unexplored natural sources of bioactive ingredients are gaining much attention since they can lead to the isolation of new compounds or bioactivities. The field of available natural sources has been further increased by including algae and, even more interestingly, microalgae. In the present study, a multidisciplinary approach has been used considering, in an integrated view, extraction, chemical composition and bioactivity of phytosterols from the microalga Dunaliella tertiolecta. A novel methodology to extract, separate and characterize microalgal-derived phytosterols has been developed. In addition, recoverable and reusable eluents have been selected in order to reduce the quantities of employed organic solvents. Finally, we addressed the question whether orally administered phytosterols reach the brain and if those interfere with the major neurotransmitter systems, such as the dopaminergic, serotoninergic and noradrenergic ones, in several brain areas of rats. Flash Liquid Chromatography has been used to separate the Total Sterol (TS) fraction, composed of twelve sterols, with a purity of 97.87% and a recovery percentage of 98%, while the "flash version" of Silver Ion Liquid Chromatography has been used to purify the most abundant phytosterols in TS, (22E,24R)- methylcholesta-5,7,22-trien-3β-ol (ergosterol) and (22E,24R)-ethylcholesta-5,7,22-trien-3β-ol (7-dehydroporiferasterol), with a purity of 97.4%. These two combined methods did not need sophisticated technologies but only cheap laboratory supplies. Moreover, the possibility of recovering and recycling the solvents used as eluents made it a cleaner process. Finally, for the first time, a neuromodulatory action of Dunaliella tertiolecta-derived phytosterols has been found in selective brain areas of rats.     

Myocardial and vascular dysfunction in systemic sclerosis: the potential role of noninvasive assessment in asymptomatic patients

Systemic sclerosis (SSc) is a multi-system disorder characterized by widespread vascular lesions and fibrosis of skin and distinct internal organs. The aim of the present study was to analyze possible associations of left ventricular (LV) myocardial function with coronary flow reserve (CFR) and endothelial function in asymptomatic patients with SSc. Thirty healthy subjects and 33 age- and sex-comparable asymptomatic SSc patients underwent standard Doppler Myocardial Imaging, Strain Rate (SR) Imaging of interventricular septum (IVS) and LV lateral wall, transthoracic CFR of left anterior descending coronary vessel, and brachial artery vasodilatation measurement. In SSc patients, LV myocardial early diastolic peak velocity, peak systolic SR and strain were both reduced in basal and middle IVS, and in basal and middle LV lateral wall (p<0.001). In addition, both CFR (p<0.0001) and endothelial flow-mediated dilatation (p<0.001) were significantly lower in SSc patients. By stepwise forward multivariate analyses, CFR (p<0.001) and endothelial function (p<0.001) were powerful independent determinants of middle LV strain of SSc patients. In conclusion, SR Imaging, transthoracic CFR and brachial artery flow-mediated dilatation are valuable non-invasive and easy-repeatable tools for detecting early LV myocardial and vascular involvement caused by SSc.     

Twelve-month azathioprine as maintenance therapy in early diffuse systemic sclerosis patients treated for 1-year with low dose cyclophosphamide pulse therapy

OBJECTIVE: To investigate the role of azathioprine in maintaining improvement after 1-year low-dose IV pulse CYC therapy in patients with early diffuse Systemic Sclerosis (dcSSc). METHODS: Thirteen patients with early dcSSc who had completed a year of treatment with low-dose IV pulse CYC underwent AZA treatment (100 mg/day) in a prospective 1-year study. Modified Rodnan skin score (mRss), Health Assessment Questionnaire-Disability Index (HAQ-DI), forced vital capacity (FVC), and diffusing lung capacity for CO (DLCO) were assessed as outcome measures. In addition, the nine organ/system Medsger et al. severity scores and the European Scleroderma Study Group (ESSG) activity index were evaluated. RESULTS: The improvement from a year of CYC therapy was maintained by AZA treatment. No outcome measures deteriorated (mRss 8.23 +/- 2.9 vs. 6.38 +/- 3.4; HAQ-DI 0.38 +/- 0.4 vs. 0.32 +/- 0.3; FVC 89.5 +/- 13.2 vs. 89.4 +/- 15.9; DLCO 73.6 +/- 14.4 vs. 75.0 +/- 19.5), nor were there any increases in any organ/system severity scores or ESSG activity index detected. CONCLUSION: This study suggests a role of AZA in maintaining the improvement induced by low dose pulse CYC in early dcSSc, making it possible a short duration of treatment at a low cumulative dose of the drug. These results, however, await confirmation in controlled studies.