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1.
Acta Pharmaceutica Sinica B ; (6): 213-226, 2023.
Article in English | WPRIM | ID: wpr-971692

ABSTRACT

There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor 4 (M4) in schizophrenia and dementia with Lewy bodies, however, a clinically validated M4 positron emission tomography (PET) radioligand is currently lacking. As such, the aim of this study was to develop a suitable M4 PET ligand that allows the non-invasive visualization of M4 in the brain. Structure-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12 - a subtype-selective positive allosteric modulator (PAM). The radiofluorinated analogue, [18F] 12, was synthesized in 28 ± 10% radiochemical yield, >37 GBq/μmol and an excellent radiochemical purity >99%. Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of [18F] 12 for the M4-rich striatum. However, in the presence of carbachol, a significant increase in tracer binding was observed in the rat striatum, which was reduced by >60% under blocking conditions, thus indicating that orthosteric ligand interaction is required for efficient binding of [18F] 12 to the allosteric site. Remarkably, however, the presence of carbachol was not required for high specific binding in the non-human primate (NHP) and human striatum, and did not further improve the specificity and selectivity of [18F] 12 in higher species. These results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP, where peak brain uptake of [18F] 12 was found in the putamen and temporal cortex. In conclusion, we report on the identification and preclinical development of the first radiofluorinated M4 PET radioligand with promising attributes. The availability of a clinically validated M4 PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.

2.
Egyptian Journal of Hospital Medicine [The]. 2017; 66: 221-226
in English | IMEMR | ID: emr-185319

ABSTRACT

Abstract: The goal of this review is to analyze the perfect mechanism for managing acute appendicitis. Both surgical and non-operative approaches are in contention as the best remedies for the appendix complications. To draw a better comparative analysis, the strengths and weaknesses of each proposed mechanism are analyzed. In the Kingdom of Saudi Arabia [KSA], both immediate and interval surgical procedure remain debatable as best remedies for acute appendicitis. To determine the suitability of both immediate and interval appendectomy against non-operative management in KSA, vast literature is analyzed to portray the strengths of each medical maneuver


Background: The primary objective of appendicitis management is to ensure early diagnosis and prevent operative management, which is risky and costly [1]. However, this goal has remained elusive due to delayed diagnosis, a characteristic that is prevalent for most people. In an analysis concerning the changing trends of appendicitis management over the past 30 years, surgery is not the only remedy for appendicitis patients [2]. Some individuals, as exhibited by numerous studies, have been able to recover without the need for surgical procedures, currently conceptualized as appendectomy. However, concentrating on the analysis by a number of scholars, it becomes evident that some delayed attention to symptoms, mainly due to patient's ignorance, makes appendectomy inevitable. As such, the most common cause of abdominal surgical emergency is appendicitis [3]. Narrowing down to the ground situation in America, not much difference is exhibited. Appendectomy remains the most significant tool at the physicians disposal when faced with relatable appendicitis dilemmas. By the time patients seek medical attention, it is already late, an aspect that motivates physicians to put into use prompt surgical procedures. The growing attention to appendicitis management is proportional to its prevalence rate. Appendicitis accounts for approximately 40,000 hospital admissions each year in England [2]. Similarly, early studies performed by English medical scholars indicated that close to 150 people from England and Wales die from acute appendicitis [4]. The prevalence rate of appendix complications is approximately seven to eight percent of the global population. Regardless of the advanced diagnostic and surgical technology, morbidity of the complication is 10%, and the mortality rate is between 1% and 5%. Despite its high prevalence, acute appendicitis is decreasing the in the US and the European region while proportionally increasing in the developing countries, mainly due to changing lifestyles [5, 6, 7].Consequently, a histopathological study on KSA in 2015 revealed that diagnosis rate of acute appendicitis was 52% while acute suppurative, acute gangrenous appendicitis and acute perforated appendicitis remained at 28%, 12.5% and 2% respectively [8]. However, it is important to acknowledge that the study was limited to one geographical area, but scientifically, the figures represent a consistent pattern. Significantly, the prevalence rate of subhepatic acute appendicitis accounted for 0.054% of Saudi Arabia's hospital population [9]. With much research being carried on the best way of handling appendicitis, this next segment of the review covers a summary of current research's perception concerning the effective medical procedure [operative vs. non-operative]. The summary section is not conclusive but rather shows a sample of analyses approaching the best way of handling appendix complications in the general population


Methods:A review of the literature was made using the most common electronic sources including: electronic database, EMBASE, MEDLINE search using

3.
Zanco Journal of Medical Sciences. 2009; 13 (1): 60-65
in English | IMEMR | ID: emr-197894

ABSTRACT

Background and Objectives: To study the correlation between etiology, sex, side and time of TMJA, to evaluate and compare two different surgical techniques and their postoperative complications


Methods: Twenty-one patients [15 female , 6 male] were treated in Rizgary Teaching Hospital in Hawler during the period May 2007-October 2008. The patients were referred from Hawler and Duhok governorates, and operated on by two surgeons each adopted one surgical technique, either gap arthroplasty with temporalis muscle flap [technique A] or horizontal ramus osteoctomy with masseter muscle flap [technique B]


Results: We found 95.65% of patients had TMJA before the age of ten years and 96% was due to trauma [57% was bilateral TMJA and 43% unilateral], technique [B] was easier and of shorter duration than technique [A] which was more functional. The most common postoperative complication was neural deficit [33.33%]. Anterior open-bite occurred in 36.3% of patients with bilateral ankylosis


Conclusions: The earlier the onset of ankylosis, the more the extent of deformity and the more complicated surgical technique was required. Both techniques were effective with good immediate out come

4.
YMJ-Yemen Medical Journal. 2001; 4 (1): 97-103
in English | IMEMR | ID: emr-58538

ABSTRACT

Aim: To determine the rate of acute conjunctivitis among patients attending K.U.H. and to detect the causative organism of acute conjunctivitis as well as the risk factors. A total of 100 Patients attending Kuwait University hospital out Patient have been examined during the period from October 1998 till September 1999. They have been examined by slit lamp and conjunctival swabs have been taken for culture and sensitivity Tests. There were 70 females, 30 male their age groups are 5 below 1 month, 35 below 10 years-10 between 10-20 years and 50 above 20 years. The causative organisms isolated were 60% streptococcus, 10%. H. influenza and 30% no bacterial growth. Their education were 60% non educated and 40% were educated in primary, secondary and higher schools. Among them 80% were complaining of poor water supply and 80% of them gave history of contact with acute conjunctivitis. The causative organisms of acute conjunctivitis were 60% streptococcus pneumonia, 10% haemophillus influenza and 30% non bacterial, the most important, risk factors were poor hygiene, less water supply and history of contact with acute conjunctivitis


Subject(s)
Humans , Male , Female , Acute Disease , Conjunctivitis/etiology , Risk Factors , Hospitals, University , Incidence , Risk Assessment
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