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Introduction: In high-grade spinal osteotomy involving large anterior column resection, restoration of the structural integrity of the posterior column at the osteotomy site can reduce postoperative instrumentation failure (IF). This study aimed to describe our technique of posterior strut bone grafting using an en bloc resected vertebral arch, which is useful for posterior column reconstruction after high-grade osteotomies during surgeries for spinal tumor and deformity in the lower lumbar spine., Technical Note: Using a posterior approach, en bloc resection of the targeted vertebral arch was performed in accordance with the surgical technique for total en bloc spondylectomy (TES). The posterior elements in the upper and lower adjacent vertebrae were separated by a significant space after vertebral body resection followed by cage insertion in TES or anterior column osteotomy followed by correction in deformity surgery. To create a new posterior column, the en bloc resected vertebral arch was placed at 90° rotation to bridge the upper and lower vertebral arches. Using this technique, an abundant amount of bone chips made from the resected vertebral elements were placed over the en bloc resected posterior arch as an additional bone graft. The technique was used in three patients who underwent TES for spinal tumors and in one patient who underwent grade 4 osteotomy for adult spinal deformity in the lower lumbar spine. One year after surgery, computed tomography showed that the structural integrity of bony fusion was successfully achieved between the en bloc resected arch and the posterior elements of the adjacent vertebrae in all patients and showed no postoperative IFs., Conclusions: This bone graft technique created new continuity of the posterior column after high-grade osteotomies in the lower lumbar spine. Bone fusion was achieved in the posterior elements to prevent IF after surgery., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest., (Copyright © 2024 The Japanese Society for Spine Surgery and Related Research.)

Complications of compressive spinal cord myelopathy and demyelinating disease can be difficult to diagnose. A 65-year-old woman gradually lost the ability to walk. Her imaging findings showed multiple spinal canal stenosis and ossification of the posterior longitudinal ligament in the cervical and thoracic spine. Some intramedullary signal changes were seen at sites distant from the spinal cord compression site. Although she underwent cervical and thoracic decompression and fusion surgery relatively early, her lower-extremity strength decreased after surgery. Her aquaporin 4 (AQP4)-antibody was found to be positive postoperatively, and she was diagnosed with NMOSD. Medical treatment for NMOSD improved her walking ability, and she finally became able to walk with a cane. In cases where there is a discrepancy between the site of strong stenosis and intramedullary signal changes, it is necessary to consider an anti-AQP4 antibody test and consultation with a neurologist., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kodama et al.)

Background: The current guidelines for the treatment of non-small cell lung cancer encourage local curative treatment for selected patients with oligometastases. This study evaluated the surgical results of total en bloc spondylectomy (TES) for isolated spinal metastases originating from lung cancer in carefully selected patients., Methods: We retrospectively reviewed 14 patients (7 men and 7 women) who underwent TES for spinal metastases originating from lung cancer between 2000 and 2017. The primary outcome measure was the postoperative overall survival time. The histological types included adenocarcinoma (n = 12), pleomorphic carcinoma (n = 1), and small cell lung carcinoma (SCLC) (n = 1 patient). We assessed postoperative survival using Kaplan-Meier analysis and the log-rank test., Results: The median postoperative survival time was 83.0 months (6-162 months) in 13 patients with non-small cell lung carcinoma (NSCLC) and 6 months in 1 patient with SCLC. The 3-, 5-, and 10-year overall survival rates in patients with NSCLC were 61.5%, 53.8%, and 15.4%, respectively. Poor postoperative performance status (PS) and Frankel grade, and preoperative irradiation to the vertebrae to be resected were significantly associated with short-term survival after TES in patients with NSCLC (p < 0.05)., Conclusions: The surgical results of TES for spinal metastases of lung cancer were relatively favorable among carefully selected patients. TES may be indicated for spinal metastases of lung cancer in patients with controlled primary lung cancer, NSCLC histology, prospect of good postoperative PS, and preferably no irradiation to the target vertebrae., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest.

Background: Total en bloc spondylectomy (TES) is one of the surgical procedures which has been recognized as a complete resection for spine tumors. Although the surgery achieves favorable local control for solitary spinal lesion, performing the procedure in the thoracic spine requires circumferential dissection around the vertebral body and bilateral rib resections which might result in decline of pulmonary function postoperatively. This study aimed to clarify whether the number of rib resections negatively impacts pulmonary function after the procedure., Methods: This study included 31 patients who underwent vertebrectomy (17 males and 14 females) with a mean age of 54.2 years. Pulmonary function testing (PFT) was performed before surgery and at 1 month, 6 months, and 1 year postoperative visits. Patients with restrictive disorders such as space occupying lesions in the lung, obstructive problems such as a history of asthma, and smoking history were excluded from this study. Associations between the number of rib resections and PFT data were analyzed based on the resected level of the thoracic spine., Results: There was a significant decrease in forced vital capacity (FVC) at 1 month (72% of preoperative value), followed by gradual recovery at 6 months (89%) and 1 year (90%). The percentage of predicted forced expiratory volume in 1 s remained stable. Patients who underwent three pairs of rib resections showed a significant decrease in the FVC (83.5% of the preoperative value) and FEV1 (82.1% of the preoperative value) compared with one or two pairs of rib resections., Conclusion: FVC decreased 1 month after vertebrectomy and returned to 90% of preoperative value at 1 year postoperatively. Three pairs of rib resections showed a significant decrease in FVC, suggesting the influence of a greater numbers of rib resections on pulmonary function., Competing Interests: Declaration of competing interest All authors declare that there are no personal or professional conflicts of interest related to the preparation and publication of this manuscript., (Copyright © 2022. Published by Elsevier B.V.)

Strengthening nursing leadership in health systems has been identified as a priority for achieving Universal Health Coverage (UHC). We aimed to analyse the characteristics of Japanese technical assistance projects for nursing human resource development in Lao People's Democratic Republic (Lao PDR) and suggest directions for future assistance. An upgrading program, as part of human resource development, was initiated in the 1990s; it has contributed to the development of nursing leaders. Moreover, technical assistance from development partners has had synergistic effects by consistently promoting the involvement of nursing leaders in administration, education, and clinical practice to establish a functional regulatory system. In resource-limited settings, the application of both edge-pulling (leadership development) and bottom-up (quality improvement of the mass population) strategies are required. From a long-term perspective, development partners should continue to invest in increasing the number and quality of nursing leaders by upgrading the courses and leadership training programs, starting from the younger generation., Competing Interests: The authors have no conflicts of interest to disclose., (2023, National Center for Global Health and Medicine.)

This study aimed to investigate the clinical outcomes of total en bloc spondylectomy (TES) for spinal metastases previously treated with radiotherapy (RT). This study enrolled 142 patients who were divided into two groups: those with and those without an RT history. Forty-two patients were selected from each group through propensity score matching, and postoperative complications, local recurrence, and overall survival rates were compared. The incidence of postoperative complications was significantly higher in the group with an RT history than in the group without an RT history (57.1% vs. 35.7%, respectively). The group with an RT history had a higher local recurrence rate than the group without an RT history (1-year rate: 17.5% vs. 0%; 2-year rate: 20.8% vs. 2.9%; 5-year rate: 24.4% vs. 6.9%). The overall postoperative survival tended to be lower in the group with an RT history; however, there was no significant difference between the two groups (2-year survival: 64.3% vs. 66.7%; 5-year survival: 47.3% vs. 57.1%). When planning a TES for irradiated spinal metastases, the risk of postoperative complications and local recurrence should be fully considered.

Total en bloc spondylectomy (TES) is an effective treatment for spinal tumors. However, its complication rate is high, and the corresponding risk factors remain unclear. This study aimed to clarify the risk factors for postoperative complications after TES, including the patient's general condition, such as frailty and their levels of inflammatory biomarkers. We included 169 patients who underwent TES at our hospital from January 2011-December 2021. The complication group comprised patients who experienced postoperative complications that required additional intensive treatments. We analyzed the relationship between early complications and the following factors: age, sex, body mass index, type of tumor, location of tumor, American Society of Anesthesiologists score, physical status, frailty (categorized by the 5-factor Modified Frailty Index [mFI-5]), neutrophil-to-lymphocyte ratio, C-reactive protein/albumin ratio, preoperative chemotherapy, preoperative radiotherapy, surgical approach, and the number of resected vertebrae. Of the 169 patients, 86 (50.1%) were included in the complication group. Multivariate analysis showed that high mFI-5 scores (odds ratio [OR] = 2.99, p < 0.001) and an increased number of resected vertebrae (OR = 1.87, p = 0.018) were risk factors for postoperative complications. Frailty and the number of resected vertebrae were independent risk factors for postoperative complications after TES for spinal tumors.

Background: Antenatal care (ANC) plays an important role in preventing low birthweight (LBW). Whereas the government of Lao People's Democratic Republic (Lao PDR) has committed to increasing the usage of ANC, little attention has been given to the early initiation of ANC. The present study assessed the influence of delayed and fewer ANC visits on LBW in the country., Methods: This is a retrospective cohort study conducted at Salavan Provincial Hospital. Study participants were all pregnant women who gave birth at the hospital between 1 August 2016 and 31 July 31 2017. Data were collected from medical records. Logistic regression analyses were performed to quantify the relationship between ANC visits and LBW. We also investigated factors associated with inadequate ANC visits: first ANC visit after the first trimester or < 4 ANC visits., Results: The mean birth weight was 2808.7 g [standard deviation: SD 455.6]. Among 1804 participants, 350 (19.4%) had babies with LBW, and 147 (8.2%) had inadequate ANC visits. In multivariate analyses, compared to participants with adequate ANC visits, those with ≥ 4 ANC visits and the first ANC visit after the second trimester, those with < 4 ANC visits, and those with no ANC visits had higher odds ratios (ORs) of LBW: 3.77 (95% confidence interval: CI = 1.66-8.57), 2.39 (95% CI = 1.18-4.83) and 2.22 (95% CI = 1.08-4.56), respectively. Younger maternal age (OR 1.42; 95% CI = 1.07-1.89), government subsidisation (OR 2.69; 95% CI = 1.97-3.68) and ethnic minority (OR 1.88; 95% CI = 1.50-2.34) were associated with increased risk of insufficient number of ANC visits after adjusting for covariates., Conclusions: Frequent and early initiation of ANC was associated with a reduction in LBW in Lao PDR. Encouraging childbearing-aged women to receive sufficient ANC at proper timing may lead to a reduction in LBW and improvement in short- and long-term health outcomes of neonates. Special attention will be needed for ethnic minorities and women in lower socioeconomic classes., (© 2023. The Author(s).)

Introduction: Long-term spinal stability after total en bloc spondylectomy (TES) is challenging. The aim of this study was to examine whether the new method could reduce the incidence of instrumentation failure (IF)., Methods: We retrospectively compared 116 patients with spinal tumors who underwent TES between 2010 and 2019 and were followed up for >1 year. IF, cage subsidence, and complications were evaluated. Propensity score matching between conventional and new method groups was performed for age, sex, body mass index, preoperative radiotherapy, number of resected vertebrae, number of instrumented vertebrae, tumor level, and follow-up period. There were 25 cases each in the conventional and new method groups. The conventional method used a titanium mesh cage for anterior reconstruction and 5.5-mm-diameter titanium alloy rods for posterior fixation. The new method used a more robust cage for anterior reconstruction, bone grafting was performed around the cage, and 6.0-mm-diameter cobalt chromium rods were used for posterior fixation. We compared the incidence of IF and cage subsidence after TES between the conventional and new method groups., Results: While 5 out of 25 patients (20.0%) in the conventional method group experienced IF, none from the new method group experienced IF. Three-year implant survival rates were 87.3% in the conventional and 100% in the new method groups. The new method group had a significantly higher implant survival rate (p<0.01). Cage subsidence was observed in 11 of 25 (44/0%) patients in the conventional method and 1 of 25 (4.0%; significantly lower, p<0.05) in the new method group., Conclusions: The new reconstruction method significantly reduced IF incidence in patients with TES., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest., (Copyright © 2023 The Japanese Society for Spine Surgery and Related Research.)

Study Design: Clinical case series., Purpose: This study aimed to report dynamization-posterior lumbar interbody fusion (PLIF), our surgical treatment for hemodialysisrelated spondyloarthropathy (HSA), and investigate patients' postoperative course within 2 years., Overview of Literature: HSA often requires lumbar fusion surgery. Conventional PLIF for HSA may cause progressive destructive changes in the vertebral endplate, leading to progressive cage subsidence, pedicle screw loosening, and pseudoarthrosis. A dynamic stabilization system might be effective in patients with a poor bone quality. Thus, we performed "dynamization-PLIF" in hemodialysis patients with destructive vertebral endplate changes., Methods: We retrospectively examined patients with HSA who underwent dynamization-PLIF at our hospital between April 2010 and March 2018. The radiographic measurements included lumbar lordosis and local lordosis in the fused segment. The evaluation points were before surgery, immediately after surgery, 1 year after surgery, and 2 years after surgery. The preoperative and postoperative radiographic findings were compared using a paired t-test. A p-value of less than 0.05 was considered significant., Results: We included 50 patients (28 males, 22 females). Lumbar lordosis and local lordosis were significantly improved through dynamization- PLIF (lumbar lordosis, 28.4°-35.5°; local lordosis, 2.7°-12.8°; p<0.01). The mean local lordosis was maintained throughout the postoperative course at 1- and 2-year follow-up (12.9°-12.8°, p=0.89 and 12.9°-11.8°, p=0.07, respectively). Solid fusion was achieved in 59 (89%) of 66 fused segments. Solid fusion of all fixed segments was achieved in 42 cases (84%). Within 2 years postoperatively, only six cases (12%) were reoperated (two, surgical debridement for surgical site infection; two, reoperation for pedicle screw loosening; one, laminectomy for epidural hematoma; one, additional fusion for adjacent segment disease)., Conclusions: Dynamization-PLIF showed local lordosis improvement, a high solid fusion rate, and a low reoperation rate within 2 years of follow-up.

Total hip arthroplasty (THA) for patients with hip osteoarthritis improves hip flexion contracture, subsequently improving spinal sagittal balance. However, in some cases, spinal sagittal imbalance develops in the course after THA, and its risk factors remain unknown. We aimed to investigate the risk factors of progressive spinal sagittal imbalance after THA. This retrospective cohort study of a prospectively maintained database included female patients aged ≥50 years who underwent THA. Before performing THA, we obtained each patient's anthropometric and muscle strength measurements and whole-spine radiographs. Three years postoperatively, patients underwent whole-spine radiography to examine changes in the spinal sagittal balance. Patients were assigned into groups on the basis of their preoperative and 3 year postoperative sagittal vertical axis (SVA) values. Patients with 3 year postoperative SVA values ≥40 mm with an increase ≥30 mm were categorized into the imbalance group; the other patients were categorized into the non-imbalance group. Of 103 patients, 11 (10.7%) were in the imbalance group. In multiple logistic regression analysis, preoperative weak abdominal trunk muscle strength (ATMS) ( p = 0.007) and small sacral slope (SS) ( p = 0.005) were significant risk factors for progressive spinal sagittal imbalance. In conclusion, risk factors for progressive spinal sagittal imbalance after THA were weak preoperative ATMS and small SS.

Potential risk factors associated with future osteoporotic vertebral fracture (OVF) were prospectively investigated in middle-aged and older adult women. We enrolled 197 female patients aged ≥50 years who were scheduled to undergo surgery for lower-extremity degenerative diseases. Patient anthropometric and muscle strength measurements, a bone mineral density measurement of the lumbar spine (L-BMD), and full-spine standing radiographs to examine the presence of old OVFs and spinopelvic sagittal parameters were obtained preoperatively. We evaluated 141 patients who underwent full-spine standing radiographs three years postoperatively to identify new OVFs. We excluded 54 patients who did not undergo a second radiographic examination and 2 with new traumatic OVFs. Univariate and multivariate analyses were performed to identify risk factors associated with new non-traumatic OVF occurrence. Ten (7.1%) patients developed new non-traumatic OVFs during the study period (fracture group). The fracture group had less abdominal trunk muscle strength, lower L-BMD, smaller sacral slopes, and larger pelvic tilt than the non-fracture group. The fracture group showed a higher prevalence of old OVFs preoperatively than the non-fracture group. Abdominal trunk muscle weakness, low L-BMD, and the presence of old OVFs were identified as significant risk factors for OVF occurrence. In middle-aged or older adult women, abdominal trunk muscle weakness, low L-BMD, and old OVFs were associated with future OVF.

The prolonged survival of metastatic cancer patients highlights the importance of the local control of spinal metastases, which reduce patient performance status. This retrospective study examined the medium to long-term outcomes of spinal metastasectomy by evaluating 124 patients who underwent metastasectomy for isolated spinal metastases (2006-2018) with a postoperative follow-up for a minimum of 3 years. The findings present information on patient demographics (i.e., performance status, location of non-spinal metastases, and history of systemic therapy) and postoperative outcomes, including perioperative complications, disease progression of non-operated metastases, and additional excisional surgeries. Additionally, postoperative survival, local tumor control in the operated spine, and maintenance of spinal reconstruction without instrumentation failure were determined using Kaplan-Meier analyses. The primary malignancy was kidney and thyroid cancer in 51 and 14 patients, respectively, low-grade sarcoma and lung cancer in 13 patients, breast cancer in 12 patients, and other malignancies in 21 patients. The 3-year and 5-year survival rates were 70% and 60%, respectively. We found that patients with thyroid cancer had the best survival results, with local tumor recurrence and instrumentation failure at 10% and 22%, respectively. These findings suggest that for certain patients with isolated and removable spine metastases, metastasectomy can improve function and survival.

Introduction: Amino acid transporters are transmembrane proteins that are known to mediate the transfer of amino acids. As one of the amino acid transporters, LAT1, which is encoded by Slc7a5, mediates the cellular uptake of the essential amino acids. Recently, most studies have focused on examining the relationship between LAT1 and skeletal formation in terms of development. However, little is known regarding the clinical features of LAT1 in the cartilage, which might result in the development of skeletal deformities such as scoliosis. Thus, the aim of this study was to investigate the expression of L-type amino acid transporter 1 (LAT1) and its solute carrier transporter 7a5 (Slc7a5) in patients with pediatric scoliosis and to compare with the relationship between LAT1 and Slc7a5 expression and their clinical features., Methods: We have prospectively recruited 56 patients who underwent corrective spinal fusion for scoliosis. The patients comprised 40 girls and 16 boys, with a mean age of 13.1 years at the time of surgery. There were 34 idiopathic scoliosis (IS) patients, whereas 22 were congenital scoliosis (CS) patients. During the surgery, an epiphyseal part of the spinous process at apical vertebra was harvested; then, LAT1 and Slc7a5 expressions in the cartilage were evaluated., Results: As per our findings, LAT1 expression was observed in the cartilage in 60.7% (34 out of 56) of the patients. LAT1 expression in IS patients was 76%, which were statistically higher compared to 36% in CS patients. When compared with LAT1 expression, no statistical difference was noted in terms of age, gender, body mass index (BMI), Cobb angle, and Risser grade. Meanwhile, the mean Slc7a5 expression in IS patients was determined to be significantly higher than that in CS patients. No significant correlation was observed between Slc7a5 expression and age, BMI, and Cobb angle., Conclusions: LAT1 and Slc7a5 expression in IS and CS patients showed significant differences. These expressions were found to be not correlated with age, stature, and severity of the deformity., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest., (Copyright © 2022 by The Japanese Society for Spine Surgery and Related Research.)

Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest.

The synthesis and molecular structure of a dimeric, mono-aluminum complex composed of two tri-lacunary α-Dawson polyoxometalates, [H 14 Al(B-α-P 2 W 15 O 56 ) 2 ] 7- (1), is described herein. The tetra- n -butylammonium salt of 1, [( n -C 4 H 9 ) 4 N] 7 [H 14 Al(B-α-P 2 W 15 O 56 ) 2 ] (TBA-1) was prepared by passing an aqueous solution of K 6 [B-α-H 3 P 2 W 15 O 59 {Al(OH 2 )} 3 ]⋅14H 2 O through an ion-exchange resin column (H + -form), followed by addition of tetra- n -butylammonium bromide. Analytically pure and colorless crystals of TBA-1 were obtained via vapor diffusion from acetonitrile/methanol at ~25 °C. Single-crystal X-ray structure analysis revealed that a six-coordinate aluminum ion was sandwiched between two tri-lacunary α-Dawson-type units, resulting in an overall C 2 h symmetry. The characterization of TBA-1 was accomplished by elemental analyses, thermogravimetric/differential thermal analyses, Fourier-transform infrared spectroscopy, and solution 31 P nuclear magnetic resonance spectroscopy. The photochromic properties of TBA-1 were also characterized in methanol under light irradiation (λ = 365 nm and ≥400 nm).

Background: There is controversy about performing cervical lymph node dissections in all middle and lower thoracic esophageal squamous cell carcinoma patients. The purpose of this study was to evaluate whether intraoperative examination of thoracic paratracheal lymph node by real-time reverse transcription-polymerase chain reaction was worthwhile for selecting patients for cervical lymph node dissection., Methods: Under informed consent, 30 middle and lower thoracic esophageal squamous cell carcinoma patients were examined for thoracic paratracheal lymph node metastasis intraoperatively by hematoxylin-eosin staining and real-time reverse transcription-polymerase chain reaction for messenger RNA encoding squamous cell carcinoma antigen. When thoracic paratracheal lymph node metastasis was found, cervical lymph node dissection was performed. If the patients had no thoracic paratracheal lymph node metastasis, a randomized study for selection of cervical lymph node dissection was performed., Results: Eleven of 30 patients with middle or lower third thoracic esophageal squamous cell carcinoma had thoracic paratracheal lymph node metastasis. Five of these 11 patients had cervical lymph node metastasis. Nineteen patients who had no metastasis in the thoracic paratracheal lymph nodes were enrolled in a randomized study. Eight of the 19 patients received cervical lymph node dissection and they were found not to have cervical lymph node metastasis. The other 11 patients did not receive cervical lymph node dissection, and there was no cervical lymph node recurrence., Conclusions: The intraoperative diagnosis of metastasis in the thoracic paratracheal lymph node may be used as an indicator for cervical lymph node dissection in middle and lower thoracic esophageal cancer patients.

The medial preoptic area (MPOA) is crucial for male sex behavior. Dopamine (DA) is released in MPOA during copulation, and contributes to the reinforcing effects of mating. The aim of the present study was to identify sensory stimuli responsible for mating-induced DA release. Specifically, we determined if chemosensory cues are essential for mating-induced MPOA DA release using in vivo microdialysis in male Syrian hamsters. Hamsters were used because chemosensory cues from the olfactory mucosa and vomeronasal organ are essential for sexual behavior in this species. Sexually experienced adult male hamsters were implanted with a microdialysis guide cannula over MPOA. At the same time, males received sham olfactory bulbectomy (Sham Bx, n = 11), bilateral bulbectomy (Bibx, n = 6), or unilateral bulbectomy (Ubx) ipsilateral (Ipsi Ubx, n = 9) or contralateral (Contra Ubx, n = 8) to the microdialysis probe. This model takes advantage of the predominantly ipsilateral projections of the olfactory bulbs. Microdialysis samples were collected from the MPOA during baseline, exposure to a receptive female, and after removal of female. Extracellular DA was measured using high-performance liquid chromatography with electrochemical detection. During mating, DA increased in MPOA of Sham Bx males (to 146.7 +/- 17.5% of baseline). Bibx males did not mate, and MPOA DA did not increase (96.1 +/- 15.8% of baseline). Although both groups of Ubx males mated to ejaculation, MPOA DA increased significantly only in Contra Ubx males (to 161.8 +/- 35.3% of baseline), and not in males with Ipsi Ubx (107.6 +/- 11.5% of baseline). The results demonstrate that chemosensory cues are essential for MPOA DA release during mating in male Syrian hamsters.

Changes in glucose availability are proposed to modulate pulsatile GnRH secretion, and at least two anatomical sites, the liver and hindbrain, may serve as glucose sensors. The present study determined the relative importance of these putative glucose-sensing areas in regulating pulsatile LH secretion in the sheep. Our approach was to administer the antimetabolic glucose analog, 2-deoxy-D-glucose (2DG) into either the hepatic portal vein or the fourth ventricle in gonadectomized females in which LH pulse frequency was high. In the first study, a catheter was placed in the ileocolic vein to determine the effects of local injection of 2DG into the hepatic portal system on the release of LH. After monitoring the pattern of LH secretion for 4 h, 2DG (250 mg/kg) was infused (500 microl/min) into the liver for 2 h. For comparison, animals were also given the same dose of 2DG into a jugular vein for 2 h. Administration of 2DG into either the hepatic portal or jugular vein reduced LH pulse frequency to the same extent. Infusion of the lower dose (50 mg/kg) locally into the hepatic portal vein did not affect plasma LH profiles. Collectively, these results are interpreted to indicate that the liver does not contain special glucose-sensing mechanisms for the glucoprivic suppression of LH pulses. In the second study, 2DG (5 mg/kg) was infused (50 l/min) for 30 min into the fourth ventricle or lateral ventricle. During the subsequent 4-h sampling period, pulsatile LH secretion was significantly suppressed, but there was no significant difference in LH pulse frequency between sites of infusion. Peripheral 2DG concentrations were not detectable after either fourth or lateral ventricle infusions, indicating that the 2DG had acted centrally to suppress LH pulses. Plasma cortisol concentrations increased more in animals infused with 2DG into the fourth ventricle than in those infused into the lateral ventricle, suggesting that 2DG infused into lateral ventricle is transported caudally into the fourth ventricle and acts within the area surrounding the fourth ventricle. Overall, these findings suggest that an important glucose-sensing mechanism is located circumventricularly in the fourth ventricle. Moreover, the liver does not appear to play an important role in detecting glucoprivic action of 2DG to suppress pulsatile LH secretion.

Administration of leptin during reduced nutrition improves reproductive activity in several monogastric species and reverses GH suppression in rodents. Whether leptin is a nutritional signal regulating neuroendocrine control of pituitary function in ruminant species is unclear. The present study examined the control of pulsatile LH and GH secretion in sheep. We determined whether exogenous leptin could prevent either the suppression of pulsatile LH secretion or the enhancement of GH secretion that occur during fasting. Recombinant human met-leptin (rhmet-leptin; 50 microg/kg BW; n = 8) or vehicle (n = 7) was administered s.c. every 8 h during a 78-h fast to estrogen-treated, castrated yearling males. LH and GH were measured in blood samples collected every 15 min for 6 h before fasting and during the last 6 h of fasting. Leptin was measured both by a universal leptin assay and by an assay specific for ovine leptin. During the fast, endogenous plasma leptin fell from 1.49 +/- 0.16 to 1.03 +/- 0.13 ng/ml. The average concentration of rhmet-leptin 8 h after leptin administration was 18.0 ng/ml. During fasting, plasma insulin, glucose, and insulin-like growth factor I levels declined, and nonesterified fatty acid concentrations increased similarly in vehicle-treated and leptin-treated animals. In vehicle-treated animals, LH pulse frequency declined markedly during fasting (5.6 +/- 0.5 vs. 1.1 +/- 0.5 pulses/6 h; fed vs. fasting; P < 0.0001). Leptin treatment prevented the fall in LH pulse frequency (5.0 +/- 0.4 vs. 4.9 +/- 0.4 pulses/6 h; P = 0.6). Neither fasting nor leptin administration altered GH pulse frequency. Fasting produced a modest increase in mean concentrations of circulating GH in control animals (2.4 +/- 0.5 vs. 3.4 +/- 0.6 ng/ml; P = 0.04), whereas there was a much greater increase in GH during leptin treatment (2.7 +/- 0.6 vs. 8.6 +/- 1.6 ng/ml; P = 0.0001). GH pulse amplitudes were also increased by fasting in control (P = 0.04) and leptin-treated sheep (P = 0.007). The finding that exogenous rhmet-leptin regulates LH and GH secretion in sheep indicates that this fat-derived hormone conveys information about nutrition to mechanisms controlling neuroendocrine function in ruminants.

This study tested the hypothesis that central mechanisms regulating luteinizing hormone (LH) secretion are responsive to insulin. Our approach was to infuse insulin into the lateral ventricle of six streptozotocin-induced diabetic sheep in an amount that is normally present in the CSF when LH secretion is maintained by peripheral insulin administration. In the first experiment, we monitored cerebrospinal fluid (CSF) insulin concentrations every 3-5 h in four diabetic sheep given insulin by peripheral injection (30 IU). The insulin concentration in the CSF was increased after insulin injection, and there was a positive relationship between CSF and plasma concentrations of insulin (r = 0.80, P < 0.01). In the second experiment, peripheral insulin administration was discontinued, and the sheep received either an intracerebroventricular (i.c.v.) infusion of insulin (12 mU/day in 2.4 ml saline) or saline (2.4 ml/day) for 5 days (n = 6) in a crossover design. The dose of insulin (i.c.v.) was calculated to approximate the increase in CSF insulin concentration found after peripheral insulin treatment. To monitor LH secretory patterns, blood samples were collected by jugular venipuncture at 10-min intervals for 4 h on the day before and 5 days after the start of i.c.v. insulin infusion. To monitor the increase in CSF insulin concentrations, a single CSF sample was collected one and four days after the start of the central infusion. The i.c.v. insulin infusion increased CSF insulin concentrations above those in saline-treated animals (P < 0.05) and maintained them at or above the peak levels achieved after peripheral insulin treatment. Central insulin infusion did not affect peripheral (plasma) insulin or glucose concentrations. LH pulse frequency in insulin-treated animals was greater than that in saline-treated animals (3.5 +/- 0.2 vs. 2.3 +/- 0.3 pulses/4 h, P < 0.01), but it was less than that during peripheral insulin treatment (4.8 +/- 0.2 pulses/4 h, P < 0.01). Our findings suggest that physiologic levels of central insulin supplementation are able to increase pulsatile LH secretion in diabetic sheep with low peripheral insulin. These results are consistent with the notion that central insulin plays a role in regulating pulsatile GnRH secretion.

This study tested the hypothesis that LH secretion is modulated by insulin and that the responsiveness to hypoinsulinemia is enhanced by sex steroids. The model was the developing male lamb (12-26 wk of age) rendered diabetic by chemically induced necrosis of insulin-secreting tissue (streptozotocin). Our approach was to monitor LH secretion under diabetic conditions, with or without insulin supplementation, either in the presence or in the absence of gonadal steroids. The first experiment determined if chronic insulin supplementation could sustain LH secretion in diabetic lambs. After documentation of the induced diabetic condition, twice-daily treatment with a long-acting insulin preparation (Lente) minimized diabetes-induced hyperglycemia, sustained growth, and maintained LH pulse frequency at levels comparable to pre-diabetic conditions. A second experiment evaluated the acute regulation of LH secretion by insulin. Twenty-four hours of insulin withdrawal decreased LH pulse frequency, increased circulating glucose levels, increased the concentration of plasma non-esterified fatty acids (NEFAs), and increased urinary output of ketones. LH pulse frequency continued to decline after 96 h of insulin withdrawal. By contrast, 24 h of insulin re-supplementation increased LH pulse frequency, reduced circulating glucose and NEFA concentrations, decreased plasma cortisol, and reduced urinary output of ketones. After 96 h of insulin re-supplementation, LH pulse frequency increased further, to levels comparable with those before insulin withdrawal. A third experiment determined if the effects of insulin withdrawal on LH secretion are influenced by the presence of gonadal steroids. The same individuals were treated with a physiologic dose of estradiol (Silastic capsule, s.c.) and subsequently monitored for changes in LH secretion in the presence and in the absence of exogenous insulin. Prior to insulin withdrawal, estradiol decreased both LH pulse frequency and pulse amplitude. Moreover, after 96 h of insulin withdrawal, estradiol potentiated the decline in LH pulse frequency (47% reduction in LH pulse frequency in the presence of estradiol versus 26% reduction in LH pulse frequency in the absence of estradiol). These findings support the contention that insulin and/or insulin-dependent changes in glucose availability modulate LH(GnRH) pulse frequency, and that such effects are potentiated by, but not dependent upon, gonadal steroids.

1. The fasting-induced suppression of LH secretion is totally dependent on steroidal milieu because the suppression is observed only in intact or ovariectomized estrogen-primed rats but not in ovariectomized animals. The following neural pathway mediating fasting-induced suppression of LH secretion has been suggested by a series of experiment: A neural signal emanating from the stomach during fasting reaches the medulla oblongata via afferent vagal nerve so as to activate the noradrenergic system projecting to the PVN: this results in an increased CRH release, and in turn the suppression of the LHRH release and then LH release. Estrogen seems to activate the neural pathway by acting on somewhere in the pathway. 2. We found that the paraventricular nucleus of the hypothalamus (PVN) and A2 region of the medulla oblongata is the estrogen feedback sites associated the dependence of the fasting-induced suppression of LH secretion on estrogen. The estrogen feedback action on the PVN does not involve an increase in norepinephrine release in the PVN. In addition, we also found that estrogen receptors are increased in the PVN and A2 region by acute fasting. Therefore, the following hypothesis is proposed: fasting first induces an transient increase in the activity of noradrenergic system at the beginning of the first dark phase after the food deprivation; this activation results in an increase in estrogen receptors in the PVN and A2 region; the increase in estrogen receptors leads to an increase in the sensitivity of noradrenergic systems to the neural inputs associated with fasting to these nuclei. 3. The response of the reproductive activity to various external stimuli including stress is modulated by ovarian steroids. The estrogen feedback action on the PVN and A2 is totally different from the so-called "negative feedback action" of estrogen that is for monitoring the ovarian condition. The novel estrogen feedback action may alter the response of neurons regulating gonadal axis to the signal associated with environmental cues such as stress.