Ketogenic diet enhances the effects of oxycodone in mice.

Opioids have been used to manage pain for thousands of years, but they have significant potential for abuse. Prescription opioids, like oxycodone, are associated with 32% of overdoses, that have reached a total of 75,673 deaths in 2021. A major challenge is maximizing their therapeutic potential while minimizing the negative side effects including opioid use disorder (OUD). The Ketogenic Diet (KD) has been reported to reduce pain and decrease the severity of alcohol use disorder, yet its effects on oxycodone responses remain unknown. KD mice displayed increased oxycodone-induced locomotor activity and enhanced antinociceptive effects of oxycodone, suggesting a dietary effect on opiate sensitivity. Male KD mice exposed to chronic oxycodone exhibited increased naloxone-induced jumps, suggesting a sex-specific effect of diet on opioid withdrawal. Consistent with this, male KD mice self-administered less oxycodone while female KD mice did not differ from controls. Finally, no effect of KD on motivation to obtain oxycodone was observed during a progressive ratio schedule. These data suggest sex-biased effects of KD on responses to opioids that should be considered and potentially leveraged in both clinical pain management and treatment of OUD.

Clinical use of tissue plasminogen activator for systemic thrombolysis in dogs and cats.

INTRODUCTION: Systemic administration of tissue plasminogen activator (tPA) is seldomly reported in dogs and cats. ANIMALS: Client-owned animals receiving tPA (2010-2020). MATERIALS AND METHODS: Medical records of dogs and cats receiving tPA for distant known/suspected thrombus were reviewed. Fourteen dog visits (24 injections) and five cat visits (six injections) were included. RESULTS: Canine known/suspected thrombus included pulmonary thromboembolism (n=6), intracardiac thrombus (n=4), aortic thrombus (n=1), cranial vena cava thrombus (n=2), and femoral and iliac veins thrombus (n=1). Various canine primary diseases were represented, but open-heart surgery was the most common cause. Median time between diagnosis/suspicion of thrombus and tPA injection was 24.5 h (range, 3-150 h). Mean total tPA dose was 1.0±0.78 mg/kg. Clinical improvement occurred in 93% of dogs. Non-fatal complications were reported in 14% of dogs. Dogs' survival to discharge was 78.6% without identifiable non-survivor characteristics. Feline known/suspected thrombus included unilateral feline aortic thromboembolism (FATE) (n=2), bilateral FATE (n=2), and right renal artery thrombus. Feline primary diseases included cardiomyopathy (n=5). Median time between diagnosis/suspicion of thrombus and tPA injection was 4 h (range, 2-17 h) and median total tPA dose was 1.0 mg/kg (range, 0.6-1.4 mg/kg).Clinical improvement occurred during 40% of the visits. All cats (n=3) with acute kidney injury (AKI) at admission developed worsening AKI and reperfusion injury. Of the remaining two visits, one developed a non-fatal AKI. Cats' survival to discharge was 40%. CONCLUSIONS: Systemic thrombolysis with tPA seems to be effective and safe in dogs. More investigation is needed in cats.

Assessment of the psychometric properties of the Spanish language version of questionnaire ICIQ-Male Lower Urinary Tract Symptoms (ICIQ-MLUTS).

OBJECTIVES: To evaluate the psychometric properties of the Spanish version of the ICIQ-Male Lower Urinary Tract Symptoms Questionnaire (ICIQ-MLUTS): Feasibility (% of completion and ceiling/ground effects), reliability (Test-retest), convergent validity (vs Bladder Control Self-Assessment Questionnaire [BSAQ] and vs International Prostate Symptom Score [I-PSS]) and criterion validity (according to presence or absence of symptoms). MATERIAL AND METHODS: This was an observational, non-interventionist and multicenter study. 223 male patients with lower urinary tract symptoms (LUTS), predominantly storage symptoms and aged 18-65, took part in the study. Patients completed the ICIQ-MLUTS (test), I-PSS and BSAQ questionnaires and referred their urinary symptoms in a single visit, with the exception of a subgroup composed by 49 patients that completed the questionnaire again 15 days after initial visit to evaluate test-retest reliability. The questionnaire includes 13 items divided in 2 sub-scales: Voiding symptoms (V) from 0-20 and Incontinence symptoms (I) from 0-24. RESULTS: Percentage of patients that completed all items: 98.84%. Ground effect is 0 and ceiling effect was under 6% in both sub-scales. Test-retest reliability: Intraclass correlation coefficient (ICC) ranged from 0.68 to 0.88, except on Delay. Kappa shows a good agreement, between 0.60 and 0.81, except for Nocturia. Convergent validity: Correlation (Spearman) between the questionnaire sub-scales scores and the rest of measures is statistically significant (P < .01 and P < .05). Criterion validity: Statistically significant differences (P < .05) between scores on ICIQ-MLUTS, from patients that refer experiencing symptoms and those who do not. CONCLUSION: The Spanish version of the ICIQ-MLUTS questionnaire shows adequate feasibility, reliability and validity.

Risk factors for Banff borderline acute rejection in protocol biopsies and effect on renal graft function.

INTRODUCTION: The interpretation and handling of Banff borderline acute rejection observed in protocol biopsies from patients with stable renal function continues to be controversial. Our objective was to identify the risk factors for borderline acute rejection on 1-year protocol biopsies and to evaluate their effect on renal graft function after 2 years' follow-up. METHODS: We included 82 kidney transplant recipients (KTR), who underwent 1-year protocol biopsies with normal or stable graft function. All KTR had follow-up of at least 2 years posttransplantation. We formed three groups: (1) KTR with a normal biopsy, (2) KTR with borderline changes, and (3) KTR with interstitial fibrosis/tubular atrophy (IF/TA). We searched for risk factors related to borderline injury. The main outcome to evaluate was renal function at 1 month, at protocol biopsy, and 2 years posttransplant. RESULTS: The 82 patients included in this study showed no differences in immunosuppression, gender, etiology of renal failure, or percentage of panel-reactive antibodies. The risk factors associated with borderline lesions were: at least one biopsy due to allograft dysfunction and acute rejection events during the first year posttransplant (P = .011 and P = .021, respectively). Increased serum creatinine and estimated glomerular filtration rate decline were greater among the borderline lesion than the normal group, but similar to patients with IF/TA. CONCLUSION: Renal function decline was greater among borderline and IF/TA groups. However, the sum of insults, and not only the borderline injury itself, produces greater declines in renal function with greater risk for graft loss.

(-)-istanbulin a.

THE TITLE COMPOUND (SYSTEMATIC NAME: 9a-hydr-oxy-3,4a,5-trimethyl-4a,6,7,8a,9,9a-hexa-hydro-4H,5H-naphtho[2,3-b]furan-2,8-dione), C(15)H(20)O(4), is a sesquiterpene lactone showing the typical eremophilanolide skeleton, which has been isolated from the plant Senecio candidans collected in the Chilean Magallanes region. The present study confirms the atomic connectivity assigned on the basis of (1)H and (13)C NMR spectroscopy, as well as the relative stereochemistry of the 4α-methyl,5α-methyl,8ß-hydr-oxy,10ß-H unit. The crystal structure is stabilized by inter-molecular O-H⋯O hydrogen bonds involving the hydr-oxy group as donor and the oxo group as acceptor, giving chains along the a axis. The absolute structure was not determined because of the lack of suitable anomalous scatters.

Stereotactic biopsy of brain stem and posterior fossa lesions in children.

Mass and cystic lesions of the posterior fossa constitute an important chapter in neurosurgical paediatric pathology. Their histological definition is essential for specific treatment. Different types of cysts, can be found besides gliomas, tuberculomas, vascular malformations, radionecrotic lesions or other masses. This paper summarises the results of an observational, descriptive, retrolective study of a group of 30 children with posterior fossa lesions seen from October 1989 to January 1997 at the Hospital Infantil de México (Children's Hospital of México). All the lesions were approached stereotactically to get biopsies and/or to drain cystic lesions. Clinical case notes were reviewed detailing different variables. It should be mentioned that in among these variables, all procedures were carried out using general endotracheal anaesthesia and that in spite of having performed the biopsy or drainage in the CT scanning suite, no infectious processes supervened. Tissue or fluid samples were obtained using the above mentioned procedure although the specimen was insufficient for histological diagnosis in one. For this case, a biopsy done afterwards by direct microsurgical exploration revealed an astrocytoma. In the rest, anaplastic astrocytomas were found in five patients, low grade astrocytomas in 11, and one case of each with the following lesions: medulloblastoma, reactive gliosis, germinoma, teratoma, tuberculoma, bacterial abscess, primitive neuro-ectodermal tumour and chronic leptomeningitis with a decreased cerebellar neuronal population. Two biopsies reported normal cerebellar tissue and in the remaining three, acellular fluid from cystic lesions was obtained. In four patients, cystic drainage was considered part of the treatment. Our results indicate that biopsies of masses and fluid drainage of cystic lesions of the posterior fossa are safe and simple methods. The empirical treatment that is sometimes used for these kinds of lesions, as well as for lesions at any other location in the central nervous system, should be abandoned.