Dopamine Receptors in Parkinson's Disease: A Meta-Analysis of Imaging Studies

Dopamine receptors are abundant along the central nigrostriatal tract and are expressed as 5 subtypes in two receptor families. In PD, compensatory changes in dopamine receptors emerge as a consequence of the loss of dopamine nerve terminals or dopaminergic pharmacotherapy. We performed a systematic review and meta-analysis of the available PET and single-photon emission computed tomography studies that have investigated dopamine receptors in PD, PSP and MSA. The inclusion criteria were studies including human PET or single-photon emission computed tomography imaging; dopamine receptor tracers (D1-like or D2-like) and idiopathic PD, PSP, or MSA patients compared with healthy controls. The 67 included D2-like studies had 1925 patients. Data were insufficient for an analysis of D1-like studies. PD patients had higher striatal binding early in the disease, but after a disease duration of 4.36 years, PD patients had lower binding values than healthy controls. Striatal D2R binding was highest in unmedicated early PD patients and in the striatum contralateral to the predominant motor symptoms. PSP and MSA-P patients had lower striatal D2R binding than PD patients (14.2% and 21.8%, respectively). There is initial upregulation of striatal D2Rs in PD, which downregulate on average 4 years after motor symptom onset, possibly because of agonist-induced effects. The consistent upregulation of D2Rs in the PD striatum contralateral to the predominant motor symptoms indicates that receptor changes are driven by neurodegeneration and loss of striatal neuropil. Both PSP and MSA patients have clearly lower striatal D2R binding values than PD patients, which offers an opportunity for differential diagnostics. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society     

Are small hospitals with small intensive care units able to treat patients with severe sepsis?

Purpose  

To find out whether mortality from sepsis is influenced by the size of the hospital and of the intensive care unit (ICU).     

The Influence of Dichloromethylene Bisphosphonate on the Healing of a Long Bone Fracture,Composition of Bone Mineral and Histology of Bone in the Rat

Abstract: The effects of dichloromethylene bisphosphonate (clodronate) on the composition of bone mineral, morphology and histology of a long bone with an artificial femoral fracture were studied in a 22 week experiment. Two hundred twenty-four female rats were allocated to dose groups of 0, 3, 10, and 30 mg/kg clodronate daily subcutaneously. Bone calcium, phosphorus and magnesium concentrations remained stable and fluoride concentration rose with time. There were no statistical differences between different groups. Clodronate did not alter the histology of the callus nor delayed the healing of the fracture. It caused mild to moderate prominence of the metaphyseal area in the fractured bone in a dose- and time-dependent manner. Serum osteocalcin levels were lowered in the treated animals dose-dependently. Other serological as well as haematological values were within normal range. Clodronate seems in this experimental arrangement to be a safe agent to administer in different pathological conditions of bone even when they are complicated by fractures of long bones.     

Orbital germ cell tumors revisited: A clinicopathological approach to classification

Orbital teratomas are unilateral, congenital germ cell tumors, which present at birth with moderate to massive proptosis, leading to exposure keratopathy. They enlarge the orbit diffusely. Primary orbital teratomas cause axial or vertical proptosis, are usually unassociated with bony defects, and do not extend outside the orbit. Recurrence is unusual after an early excision without enucleation or exenteration. Combined orbital teratomas additionally involve periorbital and intracranial spaces, cause lesser degrees of proptosis, and typically are associated with defects of orbital bones. Their intracranial part is small as compared to the orbital one. A significant risk of recurrence exists even after a combined craniotomy, orbitotomy and plastic reconstructive surgery. Intracranial teratomas with secondary orbital spread present prenatally with polyhydramnois and hydrocephalus, due to a massive primary tumor replacing parts of the brain, and typically lead to stillbirth. One orbital teratoma with malignant change has been well documented. Included twins, monsters rather than neoplasms, represent parts of a second fetus in the orbit. Orbital yolk sac carcinomas or endodermal sinus tumors are malignant neoplasms affecting children, which frequently invade periorbital and intracranial spaces, and which may respond to chemotherapy and irradiation. Finally, a teratoma or a yolk sac carcinoma may rarely present as an intraocular tumor.     

Increase in cerebral blood flow of right prefrontal cortex in man during orgasm

The functional anatomy of human emotional responses has remained poorly understood, mainly because invasive experiments in humans are unacceptable due to ethical reasons. The new functional imaging techniques such as positron emission tomography and single photon emission computed tomography have made it possible to study the neurophysiology of living humans non-invasively. We studied the regional cerebral blood flow with semi-quantitative ^99mTC-HMPAO single photon emission computed tomography in eight healthy right-handed heterosexual males during orgasm. The results showed decrease of cerebral blood flow during orgasm in all other cortical areas except in right prefrontal cortex, where the cerebral blood flow increased significantly (P < 0.005).     

Gender differences in age and BMI distributions in partial upper airway obstruction during sleep

The obstructive sleep apnea-hypopnea syndrome occurs more frequently and with higher apnea-hypopnea indices in men than in women. To investigate the gender differences we extended our respiratory analyses during sleep to cover not only periodic obstruction (apnea and hypopnea) but also nonperiodic partial upper airway obstruction during sleep and their associations with increasing age or body mass index (BMI). The clinical sleep recordings with the static-charge-sensitive bed (SCSB) and oximeter were reviewed in 233 age and BMI-matched men-women pairs. Periodic obstruction increased with increasing BMI only in men. Nonperiodic partial obstruction increased with moderate to morbid obesity in women and men after the age of 65 years. Our findings suggest that while partial upper airway obstruction increases with increasing age and BMI in both genders, men have a gender specific BMI dependent predisposition for periodic obstruction (obstructive sleep apnea). The apnea-hypopnea index is likely to underestimate the impact of sleep-disordered breathing, particularly in elderly patients.     

Engineering anthracycline biosynthesis toward angucyclines

The biosynthesis pathways of two anthracyclines, nogalamycin and aclacinomycin, were directed toward angucyclines by using an angucycline-specific cyclase, pgaF, isolated from a silent antibiotic biosynthesis gene cluster. Addition of pgaF to a gene cassette that harbored the early biosynthesis genes of nogalamycin resulted in the production of two known angucyclinone metabolites, rabelomycin and its precursor, UWM6. Substrate flexibility of pgaF was demonstrated by replacement of the nogalamycin minimal polyketide synthase genes in the gene cassette with the equivalent aclacinomycin genes together with aknE2 and aknF, which specify the unusual propionate starter unit in aclacinomycin biosynthesis. This modification led to the production of a novel angucyclinone, MM2002, in which the expected ethyl side chain was incorporated into the fourth ring.