Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder and is characterized by progressive dopaminergic and nondopaminergic neuronal loss and the presence of Lewy bodies, which are primarily composed of aggregated α-synuclein. Despite advancements in symptomatic therapies, such as dopamine replacement and deep brain stimulation, no disease-modifying therapies (DMTs) have been identified to slow or arrest neurodegeneration in patients with PD. Challenges in DMT development include disease heterogeneity, the absence of reliable biomarkers, and the multifaceted pathophysiology of PD, encompassing neuroinflammation, mitochondrial dysfunction, lysosomal impairment, and oxidative stress. Drug repositioning and repurposing strategies using existing drugs for new therapeutic applications offer promising approaches to accelerate the development of DMTs for PD. These strategies minimize time, cost, and risk by using compounds with established safety profiles. Prominent candidates include glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, ambroxol, calcium channel blockers, statins, iron-chelating agents, c-Abl inhibitors, and memantine. Although preclinical and early clinical studies have demonstrated encouraging results, numerous phase III trials have yielded unfavorable outcomes, elucidating the complexity of PD pathophysiology and the need for innovative trial designs. This review evaluates the potential of prioritized repurposed drugs for PD, focusing on their mechanisms, preclinical evidence, and clinical trial outcomes, and highlights the ongoing challenges and opportunities in this field.

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder and is characterized by progressive dopaminergic and nondopaminergic neuronal loss and the presence of Lewy bodies, which are primarily composed of aggregated α-synuclein. Despite advancements in symptomatic therapies, such as dopamine replacement and deep brain stimulation, no disease-modifying therapies (DMTs) have been identified to slow or arrest neurodegeneration in patients with PD. Challenges in DMT development include disease heterogeneity, the absence of reliable biomarkers, and the multifaceted pathophysiology of PD, encompassing neuroinflammation, mitochondrial dysfunction, lysosomal impairment, and oxidative stress. Drug repositioning and repurposing strategies using existing drugs for new therapeutic applications offer promising approaches to accelerate the development of DMTs for PD. These strategies minimize time, cost, and risk by using compounds with established safety profiles. Prominent candidates include glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, ambroxol, calcium channel blockers, statins, iron-chelating agents, c-Abl inhibitors, and memantine. Although preclinical and early clinical studies have demonstrated encouraging results, numerous phase III trials have yielded unfavorable outcomes, elucidating the complexity of PD pathophysiology and the need for innovative trial designs. This review evaluates the potential of prioritized repurposed drugs for PD, focusing on their mechanisms, preclinical evidence, and clinical trial outcomes, and highlights the ongoing challenges and opportunities in this field.

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder and is characterized by progressive dopaminergic and nondopaminergic neuronal loss and the presence of Lewy bodies, which are primarily composed of aggregated α-synuclein. Despite advancements in symptomatic therapies, such as dopamine replacement and deep brain stimulation, no disease-modifying therapies (DMTs) have been identified to slow or arrest neurodegeneration in patients with PD. Challenges in DMT development include disease heterogeneity, the absence of reliable biomarkers, and the multifaceted pathophysiology of PD, encompassing neuroinflammation, mitochondrial dysfunction, lysosomal impairment, and oxidative stress. Drug repositioning and repurposing strategies using existing drugs for new therapeutic applications offer promising approaches to accelerate the development of DMTs for PD. These strategies minimize time, cost, and risk by using compounds with established safety profiles. Prominent candidates include glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, ambroxol, calcium channel blockers, statins, iron-chelating agents, c-Abl inhibitors, and memantine. Although preclinical and early clinical studies have demonstrated encouraging results, numerous phase III trials have yielded unfavorable outcomes, elucidating the complexity of PD pathophysiology and the need for innovative trial designs. This review evaluates the potential of prioritized repurposed drugs for PD, focusing on their mechanisms, preclinical evidence, and clinical trial outcomes, and highlights the ongoing challenges and opportunities in this field.

Purpose: This study was performed to identify the effects of the alpha1A adrenoceptor antagonist on the urethral perfusion pressure (UPP), and also to assess its therapeutic potentials for female bladder outlet obstruction (BOO). Materials and Methods: A cannula was placed in the femoral artery for drug administration and systemic blood pressure monitoring in each female rat. The UPP and vesical pressure (Pves) were monitored using a triple-lumen catheter. Tamsulosin (group I), doxazosin (group II) and phentolamin (group III) were injected into female rats via the femoral cannula. Tamsulosin was also injected to male rats (group IV) for comparison with Group I. Results: After administration of tamsulosin in group I, the frequency was significantly decreased and the duration of minimal urethral relaxation with high frequency oscillations (Dhfo) was significantly prolonged. None of the parameters were significantly different compared with groups II and III, with the exception of the mean arterial blood pressure (MAP). The changes of MAP after tamsulosin were significantly lower than those after doxazosin and phentolamin. In the male rats (group IV), prior to the administration of tamsulosin, the UPP and Pves curves were similar to those of the female rats, but the maximal Pves was significantly higher than in group I. After the administration of tamsulosin to group IV, the prolongation of the frequency and Dhfo were significant. Conclusions: In the female rat urethra, the alpha1A adrenergic receptor may be a functional subtype. The alpha1A adrenoceptor antagonist was found to prolong the Dhfo and decrease the frequency of involuntary bladder contraction. It might be possible that the alpha1A adrenoceptor antagonist improves not only the obstructive symptoms, but the bladder irritative symptoms also, by prolonging the Dhfo and frequency of an involuntary bladder contraction.
Adrenergic alpha-Antagonists ; Animals ; Arterial Pressure ; Blood Pressure Monitors ; Catheters ; Doxazosin ; Female* ; Femoral Artery ; Humans ; Male ; Perfusion* ; Rats* ; Receptors, Adrenergic ; Relaxation ; Urethra ; Urinary Bladder ; Urinary Bladder Neck Obstruction

BACKGROUND: Tissue biopsy is of significant importance to the parasitic diseases. This report describes in order to know the species and frequency of human parasitic infection diagnosed by biopsy at the department of anatomical pathology, KyungHee Medical Center. Finally, we estimated the trend of parasitic diseases of tissue in a feature, in Korea. METHOD: 262(0.57%) cases of parasitic infection were reviewed for analysis of the different types of parasitic infection, 45,651 biopsied materials were submitted for routine histopathological examination during a period of 12 years from 1972 to 1983 at the department of anatomical pathology, KyungHee Medical Center. RESULTS: They consisted of 136 cases of cysticercosis, 73 clonorchiasis, 16 amebiasis, 12 paragonimiasis, 9 ascariasis, 9 sparganosis, 4 scabies, 1 taeniasis, 1 enterobiasis and 1 anisakiasis. 136 cases of cysticercosis were mainly of the skeletal muscle and subcutaneous tissue. The 73 cases of clonorchiasis occurred mainly in the liver and gallbladder. In the 16 cases of amebiasis, the liver and the rectum were the main loci. In 12 cases of paragonimiasis, pleura was the main site. CONCLUSION: The frequency of parasitic infections found in biopsied specimens was found to decrease as the years passed by, but some disease such as sparganosis showed a possible increase. Tissue biopsy is an important method for detection of tissue or ectopic parasitic infections.
Amebiasis ; Anisakiasis ; Ascariasis ; Biopsy* ; Clonorchiasis ; Cysticercosis ; Enterobiasis ; Gallbladder ; Humans ; Incidence ; Korea ; Liver ; Muscle, Skeletal ; Paragonimiasis ; Parasitic Diseases* ; Pathology ; Pleura ; Rectum ; Scabies ; Sparganosis ; Subcutaneous Tissue ; Taeniasis

BACKGROUND: Hair growth is spontaneously activated from quiescent bulge stem cells or is activated from precocious anagen. Upon spontaneous activation of hair growth or activation induced by nuclear factor of activated T cells c1 (NFATc1) inhibitors, NFATc1 expression is lost and cyclin dependent kinase (CDK4) repression is relieved. OBJECTIVE: The purpose of this study was to investigate the mechanisms of cyclosporine as a hair cycle regulator in the treatment of Alopecia areata (AA). METHODS: In this study, we planned to investigate the hair growing properties of cyclosporine in vitro conditions. Briefly, the effects of different concentrations of cyclosporine (200, 500, 1,000, 2,000 mmol) on the growth of cultured hair follicles were examined through the expression of NFATc1 and CDK4. RESULTS: NFATc1 was downregulated and CDK4 expression was upregulated especially in the bulge areas, outer root sheath and hair bulb matrix cells as the concentration of cyclosporine increased. CONCLUSION: Cyclosporine induces CDK4 expression by NFATc1 suppression, which acts to relieve repressed CDK4, resulting in hair growth. In conclusion, cyclosporine is one of the candidates as a therapeutic agent for the treatment of hair loss.
Alopecia Areata ; Cyclins ; Cyclosporine* ; Hair Follicle ; Hair* ; Phosphotransferases ; Repression, Psychology ; Stem Cells ; T-Lymphocytes

Isolated ACTH deficiency is a rare cause of secondary adrenocortical insufficiency. Adrenal crisis in isolated ACTH deficiency is less common compared to primary adrenal insufficiency, but isolated ACTH deficiency is an important cause of hypoglycemia. Recently we experienced a 41-year-old man admitted because of mental confusion. On admission, plasma glucose and sodium concentration were 1.7, 132 mmol/L, respectively. Basal plasma ACTH and cortisol levels were low and other pituitary hormone showed normal response to combined pituitary stimulation test except growth hormone. Plasma ACTH concentration remained low even after intravenous injection of ovine corticotropin releasing factor. It suggest that the defect of ACTH secretion was apparently due to intrinsic pituitary rather than hypothalamic disease. The sellar CT showed the fossa to be filled by cerebrospinal fluid. After treatment with glucocorticoid, he had no further evidence of hypoglycemia and hyponatremia. In conclusion, we report a case of isolated ACTH deficiency with empty sella.
Addison Disease ; Adrenocorticotropic Hormone ; Adult ; Blood Glucose ; Cerebrospinal Fluid ; Corticotropin-Releasing Hormone ; Growth Hormone ; Humans ; Hydrocortisone ; Hypoglycemia ; Hyponatremia ; Hypothalamic Diseases ; Injections, Intravenous ; Plasma ; Sodium

PURPOSE: We analyzed angles of defect planes of spondylolysis from coronal plane using axial computed tomography to identify the problem of 45degrees oblique plain radiograph by which we routinely has used and to suggest an appropriate radiological diagnostic tool for spondylolysis. MATERIALS AND METHODS: From January 2001 to July 2002, 84 cases of spondylolysis from 44 patients were studied. The diagnosis of spondylolysis was confirmed with axial computed tomography in all cases and angles of isthmic defect from coronal plane were measured. We intended to assess the distribution of angles of isthmic defect and analyzed the result of plain radiographs which were obtained in the direction parallel to the angle of the mean value. RESULTS: Although angles of lumbar isthmic defects have a wide distribution, the mean value was 20.9+/- 9.5degrees which was nearer to coronal plane than 45degrees oblique plane. Fifty eight cases were distributed within 23degrees from coronal plane. A diagnostic sensitivities were 88.1% in lateral view, 78.6% in 45degrees oblique view and 100% in 20degrees oblique view, so a 20degrees oblique view seemed to be more sensitive in diagnosis of lumbar isthmic defect. CONCLUSION: Because the mean angle of lumbar isthmic defects from coronal plane was about 21degrees, obliqueview with 20degrees was more appropriate and sensitive diagnostic tool for spondylolysis than oblique view with 45degrees which have been used routinely.
Diagnosis ; Humans ; Spondylolysis

BACKGROUND AND OBJECTIVES: Peritonsillar abscess (PTA) is the most common deep neck infection that occurs in adults, but until now there are so many controversies about the treatment modalities. The purpose of this study is to investigate the clinical course according to the treatment modalities for peritonsillar abscess and to evaluate the efficacy of tonsillectomy. SUBJECTS AND METHOD: Two hundred twenty-six patients with peritonsillar abscess admitted from January 1999 to October 2006. Among them, a retrospective review of medical records and additional telephone interview were performed on 151 cases. RESULTS: Among 151 cases, incision and drainage (I&D) was performed in 132 cases: 7 cases were done by aspiration and others were treated by antibiotics only. There was no significant difference in the dutarion of hospitalization between I&D, aspiration and antibiotics only (p>0.05). The incidence of recurrent PTA was only 6.6% (10/151). Tonsillectomy in PTA patients significantly reduced duration, frequency and severity of sore throat in long term follow up (p<0.05). CONCLUSION: The duration of hospitalization in PTA patients did not depend on treatment modalities. We conclude that tonsillectomy is not always necessary due to low incidence of recurrent PTA even though it improves satisfaction of PTA patients.
Adult ; Anti-Bacterial Agents ; Drainage ; Follow-Up Studies ; Hospitalization ; Humans ; Incidence ; Interviews as Topic ; Medical Records ; Neck ; Peritonsillar Abscess ; Pharyngitis ; Retrospective Studies ; Tonsillectomy

Despite the identification of Acinetobacter baumannii isolates that demonstrate susceptibility to only colistin, this antimicrobial agent was not available in Korea until 2006. The present study examined the outcomes of patients with multidrug resistant (MDR) Acinetobacter species bloodstream infection and who were treated with or without colistin as part of their regimen. The colistin group was given colistin as part of therapy once colistin became available in 2006. The non-colistin group was derived from the patients who were treated with other antimicrobial regimens before 2006. Mortality within 30 days of the onset of bacteremia occurred for 11 of 31 patients in the colistin group and for 15 of 39 patients in the non-colistin group (35.5% vs 38.5%, respectively, P = 0.80). Renal dysfunction developed in 50.0% of the 20 evaluable patients in the colistin group, but in 28.6% of the 35 evaluable patients in the non-colistin group (P = 0.11). On multivariate analysis, only an Acute Physiological and Chronic Health Evaluation II score > or = 21 was associated with mortality at 30 days. This result suggests that administering colistin, although it is the sole microbiologically appropriate agent, does not influence the 30 day mortality of patients with a MDR Acinetobacter spp. bloodstream infection.
APACHE ; Acinetobacter/*drug effects/isolation & purification ; Acinetobacter Infections/*drug therapy/mortality ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Bacteremia/*drug therapy/mortality ; Child ; Colistin/administration & dosage/*therapeutic use ; Drug Resistance, Multiple, Bacterial/*drug effects ; Female ; Humans ; Male ; Middle Aged ; Republic of Korea ; Retrospective Studies ; Risk ; Treatment Outcome