Diadenosine phosphates and S-adenosylmethionine: novel boron binding biomolecules detected by capillary electrophoresis.

There is evidence that boron has a physiological role in animals and humans, but the search for boron binding biomolecules has been difficult because useful radioactive boron isotopes do not exist. To overcome this limitation we used capillary electrophoresis to identify and quantify boron binding to biomolecules by detecting the negative charge boron imparts to ligands. The effect of molecular structure and proximal electronic charges of adenosine and molecules with adenosine moieties including S-adenosylmethionine (SAM) and diadenosine polyphosphates (Ap(n)A) were compared. The boron affinity of the test species varied with the rank order SAM congruent with Ap(6)A congruent with Ap(5)A>Ap(4)A>Ap(3)A congruent with NAD(+)>Ap(2)A>NADH congruent with 5'ATP>5'ADP>5'AMP>adenosine>3'AMP congruent with 2'AMP congruent with cAMP congruent with adenine. Test species with vicinal cis-diols bound boron; species without those moieties did not. Boron binding affinity increased when proximal cationic moieties were present. Anionic moieties remote from the cis-hydroxyl binding site also positively influenced boron binding affinity. In the Ap(n)A species, cooperative complexing of boron between the terminal ribose moieties apparently occurred. In these species boron affinity greater than expected for two monocomplexes was observed and binding affinities increased as more phosphate groups (beyond three) were present separating the terminal moieties. Our results indicate that Ap(6)A, Ap(5)A, Ap(4)A, Ap(3)A, and SAM have higher affinities for boron than any other currently recognized boron ligand present in animal tissues including NAD(+).

Ruptured intracranial aneurysm in an adolescent with Alport's syndrome--a new expression of type IV collagenopathy: case report.

BACKGROUND: Aneurysmal subarachnoid hemorrhage is uncommon in the pediatric and adolescent age groups. Collagenopathies, particularly of collagen type III and IV, have been recognized in the pathogenesis of intracranial (i.c.) aneurysms in recent studies of cerebrovascular immunoreactivity and the molecular architecture of the walls of cerebral blood vessels. Alport's syndrome is a genetic disease characterized by imperfect synthesis of type IV collagen leading to sensorineural hearing loss and hematuria. The hematuria results from an abnormal synthesis of the type IV collagen of the glomerular basement membrane. CASE DESCRIPTION: After a motor vehicle accident, this 14-year-old male driver presented with diffuse subarachnoid hemorrhage confirmed by computerized tomography. Subsequent cerebral angiography revealed a left carotid artery bifurcation aneurysm. A retrospective review of the patient's history disclosed renal biopsy-proven hereditary Alport's syndrome. The patient underwent left pterional craniotomy and clipping of the aneurysm, which had clearly ruptured. CONCLUSIONS: The authors present the first clinical observation of a ruptured cerebral aneurysm in an adolescent male with Alport's syndrome. In this case the type IV collagenopathy of Alport's syndrome may have contributed to the genesis of this adolescent's aneurysm. Intracranial aneurysms may be more common in the population of collagenopathies than previously suspected and non-invasive screening may be appropriate.

Dietary boron intakes of selected populations in the United States.

Knowledge of daily boron (B) intakes will assist researchers in establishing B requirements and elucidating the metabolic role of B in humans. B concentrations in commonly consumed foods were utilized to approximate the B intake of selected US populations. Triplicate food samples were digested at low temperatures with 16 M HNO3 and 30% H2O2, and analyzed by inductively coupled plasma spectroscopy (ICP). Milk and dairy products, juices, and beverages were the largest contributors to dietary B. Total B content of average daily diets ranged from 548 microg for toddlers (2 yr old) to 883 microg for mature males (60-65 yr old), excluding tap water contributions. Toddlers consumed 3.7 times more B than mature males when adjusted for body weight (body wt) and consumed the diet with the highest boron density (1.8 microg/kJ or 0.43 microg/kcal). Adolescent females consumed a diet with the lowest B density (1.12 microg/kJ or 0.26 microg/kcal). Food B concentrations applied to diet records (1020 microg/d) and ICP analysis of the corresponding food composites (1170 microg/d) were comparable (p < 0.05). Current estimations of B in US diets are consistent with reports in the literature stating that normal adult daily B intakes are approx 1 mg.

Regulation of enzymatic activity: one possible role of dietary boron in higher animals and humans.

It is well established that vascular plants, diatoms, and some species of marine algal flagellates have acquired an absolute requirement for boron (B), although the primary role remains unknown. Discovery of naturally occurring organoboron compounds, all ionophoric macrodiolide antibiotics with a single B atom critical for activity, established at least one biochemical role of B. The unusual nature of B chemistry suggests the possibility of a variety of biological roles for B. At physiological concentrations and pH, B may react with one N group or one to four hydroxyl groups on specific biological ligands with suitable configuration and charge to form dissociable organoboron compounds or complexes. Suitable ligands include pyridine (e.g., NAD+ or NADP) or flavin (e.g., FAD) nucleotides and serine proteases (SP). B reacts with the cis adjacent hydroxyls on the ribosyl moiety of the nucleotides or, in the serine proteases, the N on the imidazole group of histidine or the hydroxyl group on the serine moiety. Reversible inhibition by B of activity of SP or oxidoreductases that require pyridine or flavin nucleotides is well known. Therefore, a proposed essential role for B is as a regulator of relevant pathways, including respiratory burst, that utilize these enzymes.

Assessing the effects of low boron diets on embryonic and fetal development in rodents using in vitro and in vivo model systems.

To date, boron (B) essentiality has not been conclusively shown in mammals. This article summarizes the results of a series of in vitro and in vivo experiments designed to investigate the role of B in mammalian reproduction. In the first study, rat dams were fed either a low (0.04 microg B/g) or an adequate (2.00 microg B/g) B diet for 6 wk before breeding and through pregnancy; reproductive outcome was monitored on gestation day 20. Although low dietary B significantly lowered maternal blood, liver, and bone B concentrations, it had no marked effects on fetal growth or development. The goal of the second study was to assess the effects of B on the in vitro development of rat postimplantation embryos. Day 10 embryos collected from dams fed either the low or adequate B diets for at least 12 wk were cultured in serum collected from male rats exposed to one of the two dietary B treatments. Dams fed the low B diet had a significantly reduced number of implantation sites compared to dams fed the B-adequate diet. However, embryonic growth in vitro was not affected by B treatment. The aim of study 3 was to define the limits of boric acid (BA) toxicity on mouse preimplantation development in vitro. Two-cell mouse embryos were cultured in media containing graded levels of BA (from 6 to 10,000 microM). Impaired embryonic differentiation and proliferation were observed only when embryos were exposed to high levels of BA (>2000 microM), reflecting a very low level of toxicity of BA on early mouse embryonic development. Study 4 tested the effects of low (0.04 microg B/g) and adequate (2.00 microg B/g) dietary B on the in vitro development of mouse preimplantation embryos. Two-cell embryos obtained from the dams were cultured in vitro for 72 h. Maternal exposure to the low B diet for 10, 12, and 16 wk was associated with a reduction in blastocyst formation, a reduction in blastocyst cell number, and an increased number of degenerates. Collectively, these studies support the concept that B deficiency impairs early embryonic development in rodents.

Traumatic intracranial aneurysms complicating anterior skull base surgery.

Traumatic cerebral aneurysm formation following closed head injury is uncommon, although well documented in the literature. Aneurysmal development following surgical procedures on the anterior skull base is extremely rare. This article reports successful neurosurgical management of 3 cases of anterior circulation aneurysms that developed following relatively straightforward rhinological procedures. These cases illustrate the vulnerability of the vessels of the anterior circle of Willis; they also document the sites of penetration of the anterior skull base. As reported in the literature, most such aneurysms occur following transsphenoidal surgery. The clinical procedures, radiological follow-up, and the surgical management are outlined; three cases are utilized to illustrate this complication. The causes of such iatrogenic injury are discussed, with emphasis on strategies for the avoidance of such injuries.

Metabolic responses of postmenopausal women to supplemental dietary boron and aluminum during usual and low magnesium intake: boron, calcium, and magnesium absorption and retention and blood mineral concentrations.

Findings from animal studies indicate that dietary boron affects several aspects of mineral metabolism, especially when animals are subjected to nutritional stressors. Eleven postmenopausal volunteers living on a metabolic ward for 167 d (one 23-d equilibration period and six 24-d treatment periods) were fed a conventional basal diet that supplied a daily average intake of 0.36 mg B, 109 mg Mg, and < 0.10 mg A1/8400 kJ. They were given supplements of 0 (BB) or 3 mg B (SB, last two periods only), 0 (BMg) or 200 mg Mg (SMg) (with magnesium supplements held constant during the last two periods), or 0 (BAl) or 1000 mg A1 (SAl)/d. The SB treatment, compared with the BB treatment, provided a 9.0-fold increase in dietary boron but yielded only a 1.5-fold increase in plasma boron concentrations. Regardless of boron dietary treatment, fecal plus urinary excretion of boron accounted for nearly 100% of dietary boron intake with no evidence of boron accumulation over time. Lack of boron accumulation and relatively small changes in blood boron values during a substantial increase in dietary boron support the concept of boron homeostasis. In subjects fed BMg, SB decreased the percentage of dietary calcium lost in the urine but increased that percentage in volunteers fed SMg, a relation that may be important in understanding metabolic mineral disorders that perturb calcium balance. Reduced calcium absorption during SAl suggests that aluminum supplementation should be limited or at least monitored in postmenopausal women prone to excessive calcium loss. Decreased total urinary oxalate during SB in BMg subjects indicates a possible role for boron in the control of urolithiasis during low-magnesium nutriture.

Deliberations and evaluations of the approaches, endpoints and paradigms for boron, chromium and fluoride dietary recommendations.

The 10th edition (1989) of the Recommended Dietary Allowances provided estimated safe and adequate daily dietary intakes (ESADDI) for chromium and fluoride and summarized the substantial evidence for boron essentiality in animals. New endpoints, approaches and paradigms to use to formulate dietary guidance for these elements were reviewed by a discussion group that met as part of a national workshop. Deliberations of the group are summarized to facilitate future discussions on dietary guidance for these elements. The category, "provisional RDA" was recommended to replace the current ESADDI category because of the ambiguities associated with the ESADDI. A provisional RDA would be defined for a dietary substance that meets one of two sets of criteria: class 1, clear evidence of essentiality but uncertain or limited quantitative data or endpoints to define dietary requirements; and class 2, strong evidence of essentiality, and clear nutritional benefit based on reasonably certain quantitative data, but lack of clear information on function or endpoints to use for deficiency dietary requirements. A summary of background information and possible approaches for assigning provisional RDAs for boron, chromium and fluoride is presented.

Cerebral aneurysm in the HIV patient: a report of six cases.

BACKGROUND: In view of the almost certain mortality of the acquired immune deficiency syndrome (AIDS) patient, controversy may arise as to how to treat those individuals with concomitant aneurysmal disease. METHODS: We conducted a retrospective case review of six patients seen in a 1-year period, who had a history of either being positive for human immunodeficiency virus (HIV) or prior opportunistic pneumonias and who, therefore, by Centers for Disease Control definition, have frank AIDS. The patients, who were in otherwise stable health, presented with subarachnoid hemorrhage from angiographically demonstrated ruptured berry aneurysms. RESULTS: There was no increased incidence of postoperative infections and the quality of life of the surviving five patients was quite good. CONCLUSIONS: In a patient in stable health, the diagnosis of HIV infection should not necessarily preclude the established regimen for the treatment of aneurysmal disease.

Moderate copper deprivation during gestation and lactation affects dentate gyrus and hippocampal maturation in immature male rats.

The hippocampal formation (HF) is involved in higher brain functions including learning and declarative memory. The possibility that dietary copper has a role in the morphological development, and therefore the function of the HF, has received little attention. A rat model of tiered copper deficiency, initiated during gestation, was employed to determine the susceptibility of the HF, regions of which develop postnatally, to copper deficiency. At postnatal 23, pups whose dams had received either 1.8 or 1.4 mg Cu/kg diet during both gestation and lactation, compared with offspring of a group that had received 4.3 mg Cu/kg diet during both periods had, significantly more cell nuclei in the infrapyrimidal arm of the dentate gyrus. Offspring of rats fed 1.4 mg Cu/kg diet, but not those fed 1.8 mg/kg, compared with those fed 4.3 mg/kg, exhibited smaller, shorter, and narrower cell nuclei in the infrapyrimidal and suprapyrimidal arms of the dentate gyrus and smaller cell nuclei in region CA3c of the hippocampus. A fourth group (gestation, 1.8 mg Cu/kg diet; lactation, 0.9 mg Cu/kg diet) exhibited alterations less marked than those exhibited by the group fed 1.4 mg Cu/kg diet. All alterations in the groups fed low copper diets were consistent with slowed cell nuclear maturation. The findings indicate that copper is required for maturation of the dentate gyrus and hippocampus. Also, copper supplied at or below 1.8 mg/kg is insufficient for morphological maturation of the dentate gyrus and hippocampus. Because the HF is important for higher brain functions, further research is needed to determine whether the copper deficiency-induced alterations in dentate gyrus and hippocampus development are transient or permanent.

HIV status does not affect microbiologic spectrum or neurologic outcome in spinal infections.

The impact of human immunodeficiency virus (HIV) on the clinical presentations, causative organisms, and neurologic outcomes of patients with spinal infections is reviewed. Thirty-two patients with spinal epidural abscesses, vertebral osteomyelitis, or both were treated at an urban hospital over a 42-month period. Thirteen of these patients were confirmed by serologic analysis to be HIV seropositive. The diagnoses were confirmed by 30 open surgical procedures (14 anterior, 16 posterior) and seven percutaneous biopsies. Twenty-seven intraoperative cultures were positive and the remaining three patients had positive blood cultures prior to the surgical procedure. In both the HIV (+) and HIV (-) groups, Staphylococcus aureus predominated as the causative organism (overall rate: 72%). Mycobacterium tuberculosis was the second most common organism. The clinical presentations in both groups were similar with pain as the most frequent symptom and objective neurologic abnormalities on physical examination in 29 of the 32 patients (91%). The results of this analysis show that the clinical presentations and organisms cultured do not differ depending upon a concurrent HIV infection. Furthermore, the ultimate neurologic outcome of patients with spinal infections depends on their neurologic status at the time of treatment and not on their HIV status.

Transoral gunshot wounds to the atlanto-axial complex: report of five cases.

Although there has been a rise in the incidence of gunshot wounds to the spine in the United States, involvement of the upper cervical spine, i.e., the atlanto-axial complex, remains rare. Management strategies for these types of injuries come from wartime as well as civilian experience, however, they are not uniformly agreed upon. Treatment strategies are aimed at both stabilization of bony structures and preservation of neurologic function. This report documents five neurologically intact patients who sustained gunshot wounds to the atlanto-axial complex, their management, and follow-up results.

The biochemical effects of physiologic amounts of dietary boron in animal nutrition models.

This review summarizes evidence that supports working hypotheses for the roles of boron in animal model systems. It is well established that vascular plants, diatoms, and some species of marine algal flagellates have acquired an absolute requirement for boron, although the primary role of boron in plants remains unknown. Recent research findings suggest that physiologic amounts of supplemental dietary boron (PSB) affect a wide range of metabolic parameters in the chick and rat model systems. Much of the current interest in boron animal nutrition began with the initial finding that PSB stimulates growth in cholecalciferol (vitamin D3)-deficient chicks, but does not markedly affect growth in chicks receiving adequate vitamin D3 nutriture. The finding suggests that boron affects some aspect of vitamin D3 metabolism or is synergistic with vitamin D3 in influencing growth. Vitamin D3 regulates energy substrate utilization, and current research findings indicate that dietary boron modifies that regulatory function. The concentration of circulating glucose, the most thoroughly investigated metabolite to date, responds to PSB, especially during concomitant vitamin D3 deficiency. In chicks, PSB substantially alleviated or corrected vitamin D3 deficiency-induced elevations in plasma glucose concentrations. The influence of vitamin D3 on cartilage and bone mineralization is mediated in part through its role as a regulator of energy substrate utilization; calcification is an energy-intensive process. There is considerable evidence that dietary boron alleviates perturbations in mineral metabolism that are characteristic of vitamin D3 deficiency. In rachitic chicks, PSB alleviated distortion of the marrow sprouts of the proximal tibial epiphysial plate, a distortion characteristic of vitamin D3 deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary boron modifies the effects of vitamin D3 nutrition on indices of energy substrate utilization and mineral metabolism in the chick.

An experiment was designed to test part of the hypothesis that physiologic amounts of dietary boron enhance utilization of or, alternatively, compensate for, inadequate concentrations of active vitamin D metabolites to normalize energy substrate utilization and mineral metabolism. Day-old cockerel chicks were fed a ground corn, high-protein casein, corn oil-based diet (< or = 0.18 mg B/kg) supplemented with physiologic amounts of boron (as orthoboric acid) at 0 (non-PSB) or 1.4 (PSB) mg/kg and vitamin D3 (as vitamin D3 powder in corn endosperm carrier) at 3.13 (inadequate, IVD) or 15.6 (adequate, AVD) micrograms/kg. After 26 days, IVD decreased food consumption and plasma calcium concentrations and increased plasma concentrations of glucose, beta-hydroxybutyrate, triglycerides, triiodothyronine, cholesterol, and alkaline phosphatase activity. In the IVD chicks, PSB returned plasma glucose and triglycerides to concentrations exhibited by the AVD chicks and increased food consumption in both IVD and AVD chicks. Histologic findings suggested that PSB enhanced maturation of the growth plate. A ninefold increase in dietary boron yielded only a two-fold increase in plasma boron concentration and no increase in femur boron concentration, which suggests that boron is under homeostatic control. The findings suggest that boron acts on at least three separate metabolic sites because it compensates for perturbations in energy substrate utilization induced by vitamin D3 deficiency, enhances major mineral content in bone, and, independently of vitamin D3, enhances some indices of growth cartilage maturation.

Rapid bony destruction with pyogenic vertebral osteomyelitis.

We report the case of a previously healthy woman who had an extremely rapid progression of pyogenic vertebral osteomyelitis. The plain film radiographs from 1 month before admission, from the time of admission, and from her 1 year follow-up are presented. Although it is a well known fact that pyogenic vertebral osteomyelitis can evolve rapidly and that the radiographic images often lag behind the clinical symptoms, it is rare to find a case with such clear radiographic documentation. A film that was interpreted as having mild arthritic changes, 1 month before admission, progressed to one that demonstrates severe bony destruction with a kyphotic angulation of 90 degrees. The current methods of diagnosis and treatment of pyogenic vertebral osteomyelitis are reviewed.

Nonsurgical treatment of compound depressed skull fractures.

Classical treatment of compound depressed skull fractures includes debridement and closure of all scalp wounds to minimize the risk of delayed intracranial infection. In selected situations, a nonsurgical approach may prove to be equally safe. Over a 33-month period, we evaluated 1075 patients for head trauma. There were 63 patients with non-missile, compound depressed skull fractures (9 of these 63 patients have been excluded for deaths that occurred within 4 days of admission). Patients with significant intracranial hematomas or dural violations over the convexity of the brain underwent formal surgical therapy. Surgical therapy was performed on 28 patients (52%; age 33 +/- 3 years; ISS 24 +/- 2) and it consisted of craniotomy with debridement, elevation of depressed fragments, repair of dural tears, and evacuation of hematomas. Nonsurgical treatment was used if there was no evidence of violation of the dura mater and of significant intracranial hematoma. If the following criteria were satisfied, then the nonsurgical approach was employed: no evidence of exposed brain or a cerebrospinal fluid leak, no pneumocephalus related to the fracture, no depressed fragments of bone more than 1 cm below the inner table of the skull, and no gross wound contamination. Nonsurgical therapy was used on 26 patients (48%; age 34 +/- 3 years; ISS 19 +/- 2) and it consisted of wound irrigation, debridement, and closure. In all 54 patients of both subsets of patients, intravenous antibiotics were administered for 5 to 7 days. After two additional days of observation, off antibiotics, the patients were discharged. There were no infectious complications related to the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)