Parkinson’s Disease and Current Treatments for Its Gastrointestinal Neurogastromotility Effects

Purpose of Review

Gastrointestinal disturbances are seen in nearly all patients with Parkinson’s disease and lead to impaired quality of life, affect drug pharmacodynamics, and potentially worsen patient’s existing motor fluctuations, leading to further disability. Recent evidence links abnormal accumulations of α-synuclein aggregates in the periphery (gut) as seen in the cortex which causes dysfunctions impacting every level of the gastrointestinal tract from the esophagus, to the stomach, small bowel, colon, and rectum and can even predate the onset of the central neurologic disorder itself. Many treatments exist for the clinical phenotypes that result from the autonomic dysfunction and neuropathy involved in this neurodegenerative disorder.

Recent findings/summary

The treatments for the gut dysfunction seen in Parkinson’s disease (PD) depend on the specific area of the gastrointestinal tract affected. For dysphagia, behavioral therapies with speech pathology, neuromuscular electrical stimulation, or botulinum toxin injection may be helpful. For gastroparesis, domperidone may serve as an antiemetic while also blunting the hypotensive potential of Levodopa while new treatments such as ghrelin agonists may prove beneficial to help appetite, satiety, gastric emptying in those with constipation, and even improve constipation. Antibiotics such as rifaximin with poor systemic absorption may be used to treat small bacterial overgrowth also found in those with PD while the benefits of probiotics is yet to be determined. Finally, constipation in PD can be a reflection of pelvic floor dyssynergia, slow transit constipation, or both, thus treatments targeting the specific anorectal dysfunction is necessary for better outcomes.

     

High dielectric constant and high breakdown strength polyimide via tin complexation of the polyamide acid precursor

Polymer dielectrics with ultra-high charge–discharge rates are significant for advanced electrical and electronic systems. Despite the fact that polymers possess high breakdown strength, the low dielectric constant (k) of polymers gives rise to low energy densities. Incorporating metal into polyimides (PI) at the polyamic acid (PAA) precursor stage of the synthetic process is a cheap and versatile way to improve the dielectric constant of the hybrid system while maintaining a high breakdown strength. Here, we explore inclusion of different percentages of Sn as a coordinated complex in a polyimide matrix to achieve metal homogeneity within the dielectric film to boost dielectric constant. Sn–O bonds with high atomic polarizability are intended to enhance the ionic polarization without sacrificing bandgap, a measurable property of the material to assess intrinsic breakdown strength. Enhancements of k from ca. 3.7 to 5.7 were achieved in going from the pure PI film to films containing 10 mol% tin.

Polyimide with high dielectric constant and breakdown strength is synthesized via tin complexation of the polyamide acid precursor. Sn–O bonds with high atomic polarizability are intended to enhance the ionic polarization without sacrificing bandgap.     

Pulmonary Pseudallescheria boydii infection with cutaneous zygomycosis after near drowning

Pseudallescheria boydii is a ubiquitously occurring fungus. While rarely causing opportunistic infection in humans, it is the most common cause of fungal pneumonia in cases of near drowning, and is associated with high mortality. P. boydii typically causes cutaneous mycetomas but may invade the lungs or brain. P. boydii infections are difficult to treat due to amphotericin B resistance and frequent need for surgical resection. Zygomycetous infections, often referred to as "mucormycoses," usually occur in immunocompromised hosts, trauma or burn victims. Like P. boydii, these organisms are found on decaying vegetation and in soil. Zygomycetous infections generally require debridement and prolonged amphotericin B. We report a case of P. boydii pneumonia with a simultaneous brain lesion and cutaneous mucormycosis in a near drowning patient. The pneumonia responded to treatment with voriconazole and the brain lesion resolved without surgery. The cutaneous mucormycosis responded to surgery and amphotericin B. This is the first documented case of simultaneous invasive P. boydii and cutaneous mucormycosis successfully treated with dual systemic antifungal therapy and resection.     

GB virus C/hepatitis G virus infection in Indian blood donors and high-risk groups.

The hepatitis G virus (HGV) or GB virus C (GBV-C) was discovered in 1995 as a putative agent of post-transfusion, non-A-E hepatitis. The present study was carried out with the aim to find the prevalence of this virus among various subject groups at risk for parenteral transmission as well as in healthy control subjects both individually and along with other parenterally transmitted hepatitis viruses. Of the 402 subjects tested, 6.22% were positive for the HBsAg surface antigen, 7.21% were positive for HCV RNA while only 2.24% were seen to be carriers of the HGV/GBV-C RNA. All the HGV/GBV-C positive cases were either multi-transfused thalassaemic subjects or hemodialysis patients. None of the healthy control subjects showed presence of the virus. Seven of the HGV/GBV-C positive subjects showed co-infection with one or more additional virological markers. Also, of the 9 HGV/GBV-C positive subjects, 5 showed elevated ALT levels while 4 showed elevated alkaline phosphatase levels. Overall our findings seem to indicate that HGV infections generally are asymptomatic, transient and self-limiting and the virus does not seem to show a very high prevalence among the Indian population.     

Molecular epidemiology and clinical implications of TT virus (TTV) infection in Indian subjects

GOALS: This study was aimed at obtaining data on the epidemiology and clinical course of TT virus (TTV) infections among Indian subjects. BACKGROUND: The TTV is a nonenveloped DNA virus, first identified in the peripheral blood of individuals with posttransfusion hepatitis of unknown etiology. There has been much conjecture regarding the disease association of this virus. STUDY: A total of 494 serum specimens from various groups of high-risk and control subjects were screened for TTV DNA by a semi-nested PCR, using the ORF1-derived N22 primers. The sera were also screened for the HBsAg surface antigen by an ELISA, HCV RNA by a 5' NCR-based RT-PCR and GBV-C/HGV RNA by a 5' UTR-based RT-PCR. The clinical and hepatic profiles of the various subjects were also studied. Seventy-one randomly picked TTV isolates were directly sequenced and their phylogeny was studied. RESULTS: TTV showed an overall positivity rate of 45.34% with a significant higher prevalence of 52.9% among the high-risk subjects as against a prevalence of 28% among healthy control subjects (P < 0.001). Abnormal liver function profiles were frequent among TTV viremic individuals and among the acute hepatitis cases studied a higher mortality rate correlated with a superimposed TTV infection. The 71 TTV isolates sequenced were found to belong to genotype 1a being closely homologous to TTV prototype TA278. CONCLUSION: The TT virus shows a significant prevalence in the Indian population, particularly among subjects at risk for acquiring parenterally transmitted infections. Our study corroborates a putative role of the virus in the etiology of liver disease, particularly in coinfection with other agents.     

In vivo articular cartilage contact at the glenohumeral joint: preliminary report

BACKGROUND: Little is known about normal in vivo mechanics of the glenohumeral joint. Such an understanding would have significant implications for treating disease conditions that disrupt shoulder function. The objective of this study was to determine articular contact locations between the glenoid and humeral articular surfaces in normal subjects during shoulder abduction with neutral, internal, and external rotations. We hypothesized that glenohumeral articular contact is not perfectly centered and is variable in normal subjects tested under physiological loading conditions. METHODS: Orthogonal fluoroscopic images and magnetic resonance image-based computer models were used to characterize the centroids of articular cartilage contact of the glenohumeral joint at various static, actively stabilized abduction and rotation positions in five healthy shoulders. The shoulder was investigated at 0 degrees , 45 degrees , and 90 degrees abduction with neutral rotation and then at 90 degrees abduction combined with active maximal external rotation and active maximal internal rotation. RESULTS: For all the investigated positions, the centroid of contact on the glenoid surface for each individual, on average, was more than 5 mm away from the geometric center of the glenoid articular surface. Intersubject variation of the centroid of articular contact on the glenoid surface was observed with each investigated position, and 90 degrees abduction with maximal internal rotation showed the least variability. On the humeral head surface, the centroids of contact were located at the superomedial quarter for all investigated positions, except in two subjects' positions at 0 degrees abduction, neutral rotation. CONCLUSIONS: The data showed that the in vivo glenohumeral contact locations were variable among subjects, but in all individuals they were not at the center of the glenoid and humeral head surfaces. This confirms that "ball-in-socket" kinematics do not govern normal shoulder function. These insights into glenohumeral articular contact may be relevant to an appreciation of the consequences of pathology such as rotator cuff disease and instability.     

Design and synthesis of anticonvulsants from a combined phthalimide-GABA-anilide and hydrazone pharmacophore

Two series of pharmacophoric hybrids of phthalimide-GABA-anilides/hydrazones were designed and synthesized and evaluated for their anticonvulsant and neurotoxic properties. The structures of the synthesized compounds were confirmed by the use of their spectral data besides elemental analysis. Initial anticonvulsant screening was performed using intraperitoneal (i.p.) maximal electroshock-induced seizure (MES), subcutaneous pentylenetetrazole (scPTZ), subcutaneous strychnine (scSTY), and intraperitoneal picrotoxin (ipPIC)-induced seizure threshold tests. All of the compounds were ineffective in the MES test. Most of the compounds were found to be effective in the scSTY and ipPIC models and very few compounds showed protection in the scPTZ model.