Bioactive isopimarane and 3,4-seco isopimarane diterpenoids from Isodon amethystoides.

Isodon amethystoides (Lamiaceae) is a popular plant in folk medicine in the southern provinces of China. Our phytochemical investigation of the twigs and leaves of this plant led to the discovery of five new diterpenoids with isopimarane and 3,4-seco isopimarane scaffolds [isoamethinols A-E (1-5)], along with the known compound 3,4-seco isopimara-4(18),7,15-triene-3-oic acid methylester (6). The chemical structures of these compounds, including the absolute configurations of the new diterpenoids, were determined by comprehensive spectroscopic analyses and single crystal X-ray diffraction measurements. These compounds were evaluated for their biological activities against a panel of human cancer cell lines, gram-positive bacterial strains and HIV. Notably, the 3,4-seco-isopimarane isoamethinol D (4) showed toxicity to the cervical Hela cancer (Hela) cells with an IC50 value of 27.21 µM and the lung (A549) cancer cells with an IC50 value of 21.47 µM. Compound 4 also exhibited mild antimicrobial activity against the oral bacterial strain Streptococcus mutans. These findings suggested that the diterpenoids with a 3,4-seco-isopimarane diterpenoids isolated from I. amethystoides could provide a novel structure scaffold for the discovery of anticancer and antimicrobial compounds.

Sacral Nerve Stimulation in Parkinson's Disease Patients With Overactive Bladder Symptoms.

OBJECTIVE: To assess the efficacy, safety, and outcomes of sacral nerve stimulation (SNS) for Parkinson's disease (PD) patients with overactive bladder symptoms. METHODS: We retrospectively reviewed PD patients who underwent Stage I SNS. Demographics, urodynamic data, and baseline voiding function were analyzed. Efficacy and safety of treatment were determined by rate of progression to Stage II, explantation, and surgical revision. Long-term outcomes were assessed using voiding diaries and/or clinic notes. RESULTS: Sixty percent (9/15) experienced ≥50% improvement in urinary parameters and proceeded to Stage II. There was no significant difference in age, body mass index, comorbidities, PD disease duration, or levodopa equivalent daily dose between successful and nonsuccessful Stage I patients. However, 100% of female patients experienced Stage I success compared to 44% of male PD patients (P = .04). Individuals with >12-month follow-up experienced an average reduction of 6 voids/day. No patients required revision or explantation of their device at latest clinic follow-up (22.2 ± 7.8 months). Higher maximal urethral closure pressures, detrusor pressure at maximum flow rate (PdetQmax), post-void residual volume, and mean bladder outlet obstruction index were observed in the Stage I trial failures. CONCLUSION: At our institution, PD patients have a similar rate of progression to Stage II compared to the general population. SNS is an effective therapy that should be considered among the treatment options for PD patients with overactive bladder symptoms. Urodynamic parameters associated with obstruction may be predictive of SNS failure in PD patients and may help guide patient selection, however further studies are needed.

Racial and Socioeconomic Factors Influence Utilization of Advanced Therapies in Commercially Insured OAB Patients: An Analysis of Over 800,000 OAB Patients.

OBJECTIVE: To determine if racial and/or socioeconomic factors influence advanced therapy utilization for refractory overactive bladder (OAB) among the commercially insured. METHODS: We queried Optum, a national claims database, between 2003 and 2017. Non-neurogenic OAB patients were identified using ICD-9/10 diagnosis codes. Demographic and treatment data were collected, including oral medication therapies (anticholinergic, beta3 agonists), and advanced therapies (OnabotulinumtoxinA [BTX], Sacral Nerve Stimulation [SNS], percutaneous tibial nerve stimulation [PTNS]). Associations between patient sociodemographic factors and advanced therapy utilization were explored. RESULTS: Of 4,229,617 OAB patients, 807,612 (19%) received medical therapies, of which 95% received oral medications only and only 4.7% received advanced therapies. Asians had the lowest use of oral therapy use (14% vs 18%-19% in other races/ethnicities, P <0.05), and advanced therapy use (0.44% vs 0.71%-0.93%, P <0.05). Asians and Hispanics were least likely to utilize SNS therapy and most likely to use PTNS compared to Blacks and Whites. BTX use was similar between races/ethnicities (P <0.05). Female gender (OR 1.65 [CI 1.61,1.69]), younger age (<65) (OR 1.28 [1.25,1.31]), higher annual income ≥$40K (OR 1.09 [1.06,1.12]) and prior use of oral medications (OR 3.30 [3.21,3.38] for 1 medication) were significantly associated with receiving advanced therapies. Non-white race (OR 0.89 [0.87,0.91]), lower education level (less than a bachelor's degree) (OR 0.97 [0.94,0.99]), and Northeast region were associated with a lower likelihood of receiving advanced therapies (P <0.05 for all). CONCLUSION: Among commercially insured, racial and socioeconomic factors predict utilization of advanced OAB therapies, including race/ethnicity, age, gender, education level, and region.

Seasonal Variability in Vitamin D Levels No Longer Detectable in Primary Hyperparathyroidism.

CONTEXT: Seasonal variability in 25-hydroxyvitamin D [25(OH)D] and PTH levels in the general population has been associated with differences in bone turnover markers, bone density, and fracture risk. Seasonal variability in 25(OH)D and PTH levels has also been reported in primary hyperparathyroidism (PHPT). OBJECTIVE: Given the widespread use of vitamin D supplements, we sought to determine whether patients with PHPT still demonstrated seasonal variation in 25(OH)D levels. DESIGN AND SETTING: This cross-sectional study was conducted at a university medical center at a Northeastern U.S. latitude (New York, NY). PATIENTS: One hundred patients with PHPT participated in the study. OUTCOME MEASURES: We assessed vitamin D supplement use and seasonal variation in serum 25(OH)D. RESULTS: Patients had PHPT ([mean ± SD] calcium, 10.8 ± 1.0 mg/dL; PTH, 85 ± 48 pg/mL) with a mean 25(OH)D level of 29 ± 10 ng/mL. Although only one fifth of participants had vitamin D deficiency (19% < 20 ng/mL), more than half were either deficient or insufficient (54% < 30 ng/mL). Sun exposure varied by season, but there were no seasonal differences in levels of 25(OH)D, PTH, bone markers, or bone mineral density, or in the prevalence of 25(OH)D less than 20 or less than 30 ng/mL. Most of the participants (65%) took supplemental vitamin D (dose among users: mean, 1643 ± 1496 IU; median, 1000 IU daily), and supplement users had markedly better vitamin D status than nonusers (25(OH)D < 20 ng/mL: 8 vs 40%; P < .0001; < 30 ng/mL: 40 vs 80%; P = .0001; ≥ 30 ng/mL: 60 vs 20%; P = .0001). CONCLUSIONS: We found no evidence of seasonal variation in 25(OH)D levels or PHPT disease severity in the Northeastern United States. This change is likely due to widespread high vitamin D supplement intake, which has resulted in better vitamin D status among supplement users and can mask the effect of season on serum 25(OH)D levels.

Therapy of hypoparathyroidism with PTH(1-84): a prospective four-year investigation of efficacy and safety.

CONTEXT: PTH may be an effective treatment option for hypoparathyroidism, but long-term data are not available. OBJECTIVE: We studied the effect of 4 yr of PTH(1-84) treatment in hypoparathyroidism. DESIGN: Twenty-seven subjects were treated with PTH(1-84) for 4 yr, with prospective monitoring of calcium and vitamin D requirements, serum and urinary calcium, serum phosphorus, bone turnover markers, and bone mineral density (BMD). RESULTS: Treatment with PTH(1-84) reduced supplemental calcium requirements by 37% (P = 0.006) and 1,25-dihydroxyvitamin D requirements by 45% (P = 0.008). Seven subjects (26%) were able to stop 1,25-dihydroxyvitamin D completely. Serum calcium concentration remained stable, and urinary calcium and phosphorus excretion fell. Lumbar spine BMD increased by 5.5 ± 9% at 4 yr (P < 0.0001). Femoral neck and total hip BMD remained stable. At 4 yr, distal radius BMD was not different from baseline. Bone turnover markers increased significantly, reaching a 3-fold peak from baseline values at 6-12 months (P < 0.05 for all), subsequently declining to steady-state levels at 30 months. Hypercalcemia was uncommon (11 episodes in eight subjects over 4 yr; 1.9% of all values), with most episodes occurring within the first 6 months and resolving with adjustment of supplemental calcium and vitamin D. CONCLUSIONS: PTH(1-84) treatment of hypoparathyroidism for up to 4 yr maintains the serum calcium concentration, while significantly reducing supplemental calcium and 1,25-dihydroxyvitamin D requirements. Lumbar spine BMD increases without significant changes at other sites. These data provide support for the safety and efficacy of PTH(1-84) therapy in hypoparathyroidism for up to 4 yr.