Performance and design considerations for an anaerobic moving bed biofilm reactor treating brewery wastewater: Impact of surface area loading rate and temperature.

Three 4 L anaerobic moving bed biofilm reactors (AMBBR) treated brewery wastewater with AC920 media providing 680 m2 protected surface area per m3 of media. Different hydraulic retention times (HRT; 24, 18, 12, 10, 8 and 6 h) at 40% media fill and 35 °C, as well as different temperatures (15, 25 and 35 °C) at 50% media fill and 18 h HRT were examined. Best performance at 35 °C and 40% media fill was observed when HRT was 18 h, which corresponded with 92% removal of soluble COD (sCOD). Organic loading rates (OLR) above 24 kg-COD m-3d-1 decreased performance below 80% sCOD removal at 35 °C and 40% media fill. The reason was confirmed to be that surface area loading rates (SALR) above 50 g-sCOD m-2d-1 caused excessive biofilm thickness that filled up internal channels of the media, leading to mass transfer limitations. Temperature had a very significant impact on process performance with 50% media fill and 18 h HRT. Biomass concentrations were significantly higher at lower temperatures. At 15 °C the mass of volatile solids (VS) was more than three times higher than at 35 °C for the same OLR. Biofilms acclimated to 25 °C and 15 °C achieved removal of 80% sCOD at SALR of 10 g-sCOD m-2d-1 and 1.0 g-sCOD m-2d-1, respectively. Even though biomass concentrations were higher at lower temperature, biofilm acclimated to 25 °C and 15 °C performed significantly slower than that acclimated to 35 °C.

Removal of Soluble Phosphorus from Surface Water Using Iron (Fe-Fe) and Aluminum (Al-Al) Electrodes.

The removal of soluble phosphorus using iron and aluminum electrodes was studied in water samples from the Red River, a hyper-eutrophic stream in Winnipeg, Canada. Four trials were conducted: (I) mixed batch with 150-900 mA applied for 1 min to 1 L, (II) stagnant batch with 600-900 mA applied for 1 min to 1 L, and (III and IV) continuously stirred-tank reactor with 6.25-10 min hydraulic retention times and constant 900 mA. Maximum soluble phosphorus removals of 70-80% were observed in mixed batch, and there was no significant difference between aluminum and iron electrodes (P value of 0.0526-0.9487). Aluminum electrodes performed significantly worse than iron electrodes under higher hydraulic loads, with iron removing >70% soluble phosphorus and aluminum <40% (P values of 0.0035-0.0143). The estimated cost of consumables, reported per million liters of water treated, to remove 70% soluble phosphorus from eutrophic waters with 0.35 g m-3 soluble phosphorus would include 5-17.5 USD electricity costs and material costs of 5.3-12.2 USD for iron and 39.2 USD for aluminum.

Aggregation of Human Mesenchymal Stromal Cells Eliminates Their Ability to Suppress Human T Cells.

Mesenchymal stromal cells (MSCs) are administered locally to treat sites of inflammation. Local delivery is known to cause MSCs to aggregate into "spheroids," which alters gene expression and phenotype. While adherent MSCs are highly efficient in their inhibition of T cells, whether or not this property is altered upon MSC aggregation has not been thoroughly determined. In this study, we discovered that aggregation of MSCs into spheroids causes them to lose their T cell-suppressive abilities. Interestingly, adding budesonide, a topical glucocorticoid steroid, alongside spheroids partially restored MSC suppression of T cell proliferation. Through a series of inhibition and add-back studies, we determined budesonide acts synergistically with spheroid MSC-produced PGE2 to suppress T cell proliferation through the PGE2 receptors EP2 and EP4. These findings highlight critical differences between adherent and spheroid MSC interactions with human immune cells that have significant translational consequences. In addition, we uncovered a mechanism through which spheroid MSC suppression of T cells can be partly restored. By understanding the phenotypic changes that occur upon MSC aggregation and the impact of MSC drug interactions, improved immunosuppressive MSC therapies for localized delivery can be designed.

Dose and duration of interferon γ pre-licensing interact with donor characteristics to influence the expression and function of indoleamine-2,3-dioxygenase in mesenchymal stromal cells.

Human mesenchymal stromal cells (MSCs) are a leading cell therapy candidate for the treatment of immune and inflammatory diseases due to their potent regulation of immune cells. MSC expression of indoleamine-2,3-dioxygenase (IDO) upon interferon γ (IFNγ) exposure has been proposed as both a sentinel marker and key mediator of MSC immunomodulatory potency. Rather than wait for in vivo exposure to cytokines, MSCs can be pre-licensed during manufacturing to enhance IDO expression. In this study, we systematically examine the relative role that the dose of IFNγ, the duration of pre-licensing and the donor of origin play in dictating MSC production of functional IDO. We find that across three human MSC donors, MSCs increase their expression of IDO in response to both increased dose of IFNγ and duration of pre-licensing. However, with extended pre-licensing, the expression of IDO no longer predicts MSCs ability to suppress activated peripheral blood mononuclear cells. In addition, pre-licensing dose and duration are revealed to be minor modifiers of MSCs inherent potency, and thus cannot be manipulated to boost poor donors to the levels of high-performing donors. Thus, the dose and duration of pre-licensing should be tailored to optimize performance of specific donors and an emphasis on donor selection is needed to realize significant benefits of pre-licensing.

Nature vs. Nurture: Defining the Effects of Mesenchymal Stromal Cell Isolation and Culture Conditions on Resiliency to Palmitate Challenge.

As MSC products move from early development to clinical translation, culture conditions shift from xeno- to xeno-free systems. However, the impact of isolation and culture-expansion methods on the long-term resiliency of MSCs within challenging transplant environments is not fully understood. Recent work in our lab has shown that palmitate, a saturated fatty acid elevated in the serum of patients with obesity, causes MSCs to convert from an immunosuppressive to an immunostimulatory state at moderate to high physiological levels. This demonstrated that metabolically-diseased environments, like obesity, alter the immunomodulatory efficacy of healthy donor MSCs. In addition, it highlighted the need to test MSC efficacy not only in ideal conditions, but within challenging metabolic environments. To determine how the choice of xeno- vs. xeno-free media during isolation and expansion would affect future immunosuppressive function, umbilical cord explants from seven donors were subdivided and cultured within xeno- (fetal bovine serum, FBS) or xeno-free (human platelet lysate, PLT) medias, creating 14 distinct MSC preparations. After isolation and primary expansion, umbilical cord MSCs (ucMSC) were evaluated according to the ISCT minimal criteria for MSCs. Following baseline characterization, ucMSC were exposed to physiological doses of palmitate and analyzed for metabolic health, apoptotic induction, and immunomodulatory potency in co-cultures with stimulated human peripheral blood mononuclear cells. The paired experimental design (each ucMSC donor grown in two distinct culture environments) allowed us to delineate the contribution of inherent (nature) vs. environmentally-driven (nurture) donor characteristics to the phenotypic response of ucMSC during palmitate exposure. Culturing MSCs in PLT-media led to more consistent growth characteristics during the isolation and expansion for all donors, resulting in faster doubling times and higher cell yields compared to FBS. Upon palmitate challenge, PLT-ucMSCs showed a higher susceptibility to palmitate-induced metabolic disturbance, but less susceptibility to palmitate-induced apoptosis. Most striking however, was that the PLT-ucMSCs resisted the conversion to an immunostimulatory phenotype better than their FBS counterparts. Interestingly, examining MSC suppression of PBMC proliferation at physiologic doses of palmitate magnified the differences between donors, highlighting the utility of evaluating MSC products in stress-based assays that reflect the challenges MSCs may encounter post-transplantation.

Time for a Time Window Extension: Insights from Late Presenters in the ESCAPE Trial.

BACKGROUND AND PURPOSE: The safety and efficacy of endovascular therapy for large-artery stroke in the extended time window is not yet well-established. We performed a subgroup analysis on subjects enrolled within an extended time window in the Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial. MATERIALS AND METHODS: Fifty-nine of 315 subjects (33 in the intervention group and 26 in the control group) were randomized in the ESCAPE trial between 5.5 and 12 hours after last seen healthy (likely to have groin puncture administered 6 hours after that). Treatment effect sizes for all relevant outcomes (90-day mRS shift, mRS 0-2, mRS 0-1, and 24-hour NIHSS scores and intracerebral hemorrhage) were reported using unadjusted and adjusted analyses. RESULTS: There was no evidence of treatment heterogeneity between subjects in the early and late windows. Treatment effect favoring intervention was seen across all clinical outcomes in the extended time window (absolute risk difference of 19.3% for mRS 0-2 at 90 days). There were more asymptomatic intracerebral hemorrhage events within the intervention arm (48.5% versus 11.5%, P = .004) but no difference in symptomatic intracerebral hemorrhage. CONCLUSIONS: Patients with an extended time window could potentially benefit from endovascular treatment. Ongoing randomized controlled trials using imaging to identify late presenters with favorable brain physiology will help cement the paradigm of using time windows to select the population for acute imaging and imaging to select individual patients for therapy.

Bradycardia during sleep apnea. Characteristics and mechanism.

To determine the characteristics of and mechanisms causing the bradycardia during sleep apnea (SA), both patients with SA and normals were studied. Evaluation of six consecutive SA patients demonstrated that bradycardia occurred during 95% of all apneas (central, obstructive, and mixed) and became marked with increased apnea length (P less than 0.01) and increased oxyhemoglobin desaturation (P less than 0.01). Heart rate slowed 9.5 beats per minute (bpm) during apneas of 10-19 s in duration, 11.4 bpm during 20-39s apneas, and 16.6 bpm during 40-59-s apneas. Sleep stage had no effect unexplained by apnea length or degree of desaturation. Oxygen administration to four SA patients completely prevented the bradycardia although apneas lengthened (P less than 0.05) in three. Sleeping normal subjects did not develop bradycardia during hypoxic hyperpnea but, instead, HR increased with hypoxia in all sleep stages, although the increase in HR was not as great as that which occurred while awake. Breath holding in awake normals did not result in bradycardia during hyperoxia (SaO2 = 99%), but was consistently (P less than 0.01) associated with heart rate slowing during room air breath-holds (-6 bpm) at SaO2 = 93%, with more striking slowing (-20 bpm) during hypoxic breath-holds (P less than 0.01) at SaO2 = 78%. Breath holding during hyperoxic hypercapnia had no significant effect on rate. Breath holding in awake SA subjects demonstrated similar findings. We conclude that the bradycardia of SA is a consistent feature of apnea and results from the combined effect of cessation of breathing plus hypoxemia.

Granulation of activated sludge under low hydrodynamic shear and different wastewater characteristics.

Five reactors were operated with low upflow superficial air velocities (0.41cmmin-1) in order to observe granulation on synthetic wastewaters with different characteristics: 1) 340mg-CODL-1; 2) 630mg-CODL-1; and 3) 1300mg-CODL-1. Stable granulation was only observed under low hydrodynamic shear for low-strength wastewater. 55-70% of soluble chemical oxygen demand (COD) was utilized before aeration and 91% COD, 62% total nitrogen (TN), and 96% total phosphorus (TP) were removed from the low-strength wastewater. Although medium-strength wastewater did generate granules they rapidly acquired a filamentous surface layer that resulted in decreased performance and loss of nitrification. 94% COD, 30% TN, and 85% TP were removed from the medium-strength wastewater. The high-strength wastewater did not develop granules and 85% COD was removed. Results demonstrated that high shear force was not required for granulation. Rather, granulation depended on multiple parameters to out-select rapidly growing aerobic microorganisms.

Tri-Calciphor (16,16-dimethyl-15-dehydroprostaglandin B1 trimer)-mediated mitochondrial Ca2+ movements: modulation by phosphate.

The trimeric derivative of 16,16-dimethyl-15-dehydroprostaglandin B1 (termed tri-Calciphor), which protects tissues against ischemic damage, induced Ca2+ efflux and swelling in mitochondria in the absence of phosphate, Mg2+ and ATP. When glutamate/malate rather than succinate was the substrate, higher tri-Calciphor concentrations were required for the ionophoretic activity. Ca2+ efflux and mitochondrial swelling induced by tri-Calciphor were completely inhibited by ATP, phosphate and Mg2+ added together, and partially inhibited with phosphate plus either ATP or Mg2+. Between 0 and 7 microM added Ca2+ and in the presence of phosphate, ATP and Mg2+, tri-Calciphor stimulated the uptake of Ca2+ by mitochondria and increased the efficiency of buffering of extramitochondrial Ca2+. Thus, depending on the assay conditions, two different effects involving Ca2+ movements and mitochondria are observed with tri-Calciphor.

Calcium ionophoretic activity of chemically synthesized oligomeric derivatives of prostaglandin B1.

Chemically synthesized dimers, trimers and tetramers of 15-dehydroprostaglandin B1 and 16,16'-dimethyl-15-dehydroprostaglandin B1 facilitate the release of Ca2+ from isolated rat liver mitochondria. The parent monomeric prostaglandins had no significant activity. The rate of release was stimulated by exogenous K+ or Na+, suggesting an antiport exchange of monovalent cations for intra-mitochondrial Ca2+. The activity depended upon the presence of ruthenium red, which prevented recycling of Ca2+; comparison of the activity with A23187 and carbonyl cyanide p-trifluoromethoxyphenylhydrazone indicated that the prostaglandin B1 oligomers were functioning as ionophores and the release of Ca2+ was not caused by an uncoupling of oxidative phosphorylation. The oligomers caused a major decrease in the membrane potential but only when the mitochondria were preloaded with exogenous Ca2+, and even then, the Ca2+ efflux was completed before the membrane potential decreased to less than 90 mV. The oligomeric molecules were able to form supramolecular aggregates in the presence of Ca2+ as detected by light scattering. They extracted Ca2+ into an organic phase, and translocated Ca2+ from one aqueous domain to another across an organic barrier; K+ and Na+ modulated these processes. The prostaglandin B1 derivatives also translocated Rb+ from one aqueous phase to another across an organic barrier when Ca2+ was translocated.

Extracellular ATP inhibits agonist-induced mobilization of internal calcium in human platelets.

Our previous studies have demonstrated that platelets possess ATP purinergic receptors in addition to the ADP, P2T, receptor. Occupancy of the P2 receptor by ATP inhibited agonist-induced platelet aggregation. This study demonstrated that the mechanism of inhibition may involve ATP inhibition of agonist-induced mobilization of internal calcium. Within the cardiovascular system, the ATP inhibition of calcium mobilization is unique to platelets. All other cell types in the cardiovascular system, where calcium mobilization is affected by extracellular ATP, responded with an increased mobilization as opposed to inhibition. The platelet inhibitory response to ATP was enhanced by the addition of an ATP generating system, creatine phosphate/phosphocreatine kinase. ATP and ATP analogues were found to inhibit calcium mobilization with a rank order of alpha beta-methylene ATP, beta gamma-methylene ATP approximately ATP > benzoyl ATP > 2 methylthio ATP which is a characteristic of P2x-like receptors. The inhibitory effect of ATP could be abrogated by prolonged treatment of platelets with the P2x desensitizing agent, alpha beta-methylene ATP. Also, UTP and CTP were approximately as effective inhibitors as ATP while GTP was not. ATP competition with ADP for the P2T receptor was excluded in studies with platelets derived from an aspirin-treated individual which were essentially insensitive to ADP. The agonist-induced calcium mobilization and inhibition by ATP occurred with the thromboxane A2 mimetic, U46619, collagen and thrombin; however, the kinetics of mobilization varied somewhat with the different agonists. The responses to extracellular ATP were independent of extracellular Ca2+, where 1 mM calcium or 0.3 mM EGTA was added to the reaction mixture. The inhibition of calcium mobilization coupled to inhibition of platelet aggregation by extracellular ATP may serve an important physiologic role. ATP, released from activated platelets at localized sites of vascular injury, may help to limit the size of the platelet plug-clot that, if left unregulated, could occlude the injured blood vessel.

Neuro-Behçet's disease: factors hampering proper diagnosis.

We reviewed the clinical course of nine patients with neuro-Behçet's disease to assess difficulties in making this diagnosis. Factors delaying proper diagnosis included lack of accurate history and physical examination, lack of recognition of an underlying systemic syndrome and its relationship to the neurologic symptoms, presence of intermittently normal CSF studies, and use of noncontrasted neuroimaging techniques.

Initial inhibition and recovery of protein synthesis in cycloheximide-treated hepatocytes.

Previous studies conducted with intact rats had demonstrated that protein synthesis was reversibly inhibited by cycloheximide. Polysome aggregation occurred during inhibition with a return to normal during recovery. Suggesting that the block of translational activity involved termination and release of polypeptides. This study involving freshly isolated hepatocytes was undertaken to clarify the mechanism of the biphasic response to cycloheximide. Cycloheximide at 1 microM inhibited [3H]leucine incorporation into both cellular and secreted proteins by at least 86%, without having deleterious effects on membrane integrity as indicated by trypan blue uptake and lactate dehydrogenase (LDH) (EC 1.1.1.27) release. After removal of cycloheximide, incorporation of labeled amino acids into cellular protein and protein secreted into the medium returned to control levels. Kinetically, incorporation into secreted protein exhibited a lag of 30-45 min, indicating that a longer recovery period for restoration of proteosynthetic ability is required for membrane-bound polysomes. During the first 100 min of the recovery period, 30% of the cellular protein, which had been prelabeled during cycloheximide inhibition, was secreted into the medium; treated cells, however, secreted prelabeled protein at a lower initial rate. To elucidate the mechanism of action of cycloheximide, the content of the cytoplasmic ribonucleoprotein complexes (RPC), polysome size classes, and the distribution of radioactivity among the various ribosome classes were determined during inhibition and recovery. Larger size class polysomes (7+) were increased by cycloheximide treatment and remained increased during recovery. During inhibition, there was enhanced [3H]leucine labeling with increasing polysome size, implicating termination as the rate-limiting step, whereas during the recovery phase the labeled nascent polypeptides were removed from the ribonucleoprotein complex at a 3- to 4-fold greater rate than control, indicating an accelerated release of completed proteins.

Modification of protein synthetic components by aflatoxin B1.

Molecular sites of perturbation by the hepatocarcinogen aflatoxin B1 (AFB1) in the protein synthesis initiation complex were assessed using isolated hepatocytes and a cell-free activating system containing microsomes and cytoplasmic ribonucleoprotein complexes (cRPC). Ribosomal proteins showed no detectable modification by the toxin in either system. With hepatocytes, initiation factors demonstrated only slight modification by AFB1. RNAs from both hepatocytes and the cell-free system with microsomes and cRPC were modified, with poly(A)-containing RNA exhibiting at least a 5-fold higher modification than poly(A)-lacking RNA. The poly(A)-lacking RNAs were modified in the order 28S rRNA greater than 18S rRNA greater than 5-6S rRNA greater than 4S tRNA. Guanine was the target base of AFB1, but only 10% of the AFB1-GMP adducts were on guanines located in a poly(G) region. These results suggest that guanine modification in RNAs may be responsible for the observed inhibition of translational initiation by AFB1 to a greater extent than modification of either ribosomal intrinsic or associated proteins.

Studies of the cation binding properties of an oligomeric derivative of prostaglandin B1.

The ionophoretic activity of PGBx, an oligomeric mixture synthesized from 15-dehydro PGB1, with different cations was measured using arsenazo III-entrapped liposomes. The order of ionophoretic activity was Zn2+ greater than Co2+ greater than Mn2+ greater than Cu2+ greater than Ca2+ greater than Ba2+ greater than Sr2+ greater than Mg2+. The intrinsic fluorescence of PGBx was quenched by the binding of divalent cations as well as by La3+ and H+. Quenching by K+ and Na+ was minimal. The order of quenching strength of divalent cations was Zn2+ greater than Co2+ greater than Cu2+ = Mn2+ greater than Ca2+ greater than Ba2+ greater than Sr2+ greater than Mg2+. Binding affinities of these cations determined by a murexide indicator method were in good agreement with that determined by the fluorescence quenching reaction. The cation binding affinity of PGBx in aqueous solutions correlates with the ionophoretic activity in liposomes. The binding affinity for K+ was estimated from the inhibition by K+ of Ca2+ binding by PGBx. Although PGBx has a lower selectivity for divalent cation binding than the ionophore A23187, the characteristics of the binding affinity of these two compounds for various ions were similar. The pK of PGBx as determined by fluorescence quenching was 6.7. The molecular weight of the divalent cation binding unit was estimated to be about 680, with each PGBx molecule having three such binding sites. The binding of Ca2+ to such a site is one-to-one.

Neuroprotective activity of dimer of 16,16'-dimethyl-15-dehydroprostaglandin B1 (di-Calciphor) in cerebral ischemia.

Post-ischemic treatment of di-Calciphor (16,16'-dimethyl-15- dehydroprostaglandin B1) significantly improves animal survival and prevents ischemia-induced neurodegeneration of vulnerable forebrain regions assessed with histochemical and biochemical techniques in gerbils. Neuronal degeneration seen by Cresyl violet staining and silver impregnation in the CA1 sector of the hippocampus and the dorso-lateral sector of the striatum was significantly reduced in animals treated with di-Calciphor. In addition, the early onset of selective degradation of calpain I substrates spectrin and microtubule-associated protein (MAP2) in these same vulnerable regions was prevented. The lack of adverse side effects may facilitate the potential therapeutic use of this drug in preventing neuronal damage caused by stroke.

Treatment of severe brain ischemia with di- and tri-Calciphor (dimer and trimer of 16,16'-dimethyl prostaglandin B1).

Following 20 min occlusion of both carotid arteries, female gerbils were subjected to treatment with di- or tri-Calciphor (dimer or trimer of 16,16'-dimethyl prostaglandin B1). Dimer was injected i.p. at 5 and 10 mg/kg at 5 min and again at 24 h, 30 min and 24 h, 60 min and 24 h or 180 min and 24 h postischemia (N = 25/group). Trimer was given i.p. at 5, 10 or 15 mg/kg at 5 min and 24 h postischemia (N = 25/group.) The controls (N = 25) were injected with the vehicle. Neurological status and postischemic survival of the animals were monitored for 14 days postischemia. Survival of the treated gerbils was significantly improved following the treatment with either di- or tri-Calciphor administered at 10 mg/kg at 5 min and 24 h postischemia (36 vs. 68% di- and 64% tri-Calciphor, P less than 0.05), and with di-Calciphor at 5 mg/kg at 180 min and 24 h postischemia (64%). All other treatment regimens with either drug resulted in a numerical, statistically insignificant improvement. In addition, treatment with either drug reduced the intensity of postischemic neurological impairment. Treatment with di-Calciphor injected at 10 mg/kg at 5 min and 24 h post 20 min ischemia substantially reduced the period of postischemic locomotor hyperactivity. The drug had no impact on either body temperature or blood pressure. There is evidence that the effects of Calciphor may be mediated via calcium regulatory mechanisms. The results of the present study are discussed in the light of such possibility.

MK-801 is neuroprotective but does not improve survival in severe forebrain ischemia.

The effects of MK-801 on postischemic recovery, survival and neuronal preservation in the cortex, hippocampus and striatum were studied in Mongolian gerbils. The drug was administered 30 min prior to 20 of min forebrain ischemia induced by bilateral ligation of the carotids. Neurological recovery and survival were monitored for 7 days. At the end of the monitoring period neuronal damage was analyzed in the brains of the survivors in both groups. Treatment with MK-801 did not improve either neurological recovery or end-point survival. However, significant (P < 0.01) neuronal protection was observed in the hippocampi and striata of the drug treated animals while cortical neurons were not significantly protected. These findings demonstrate that protection against ischemic neuronal damage can be observed without concomitant improvement in either postischemic neurological recovery or survival. Protection of selectively vulnerable brain regions, often used as the predictor of the therapeutic potential of an agent, does not appear to correlate well with postischemic survival in this animal model of ischemia.

A novel treatment of global cerebral ischaemia with a glycine partial agonist.

Chronic treatment of gerbils with 1-aminocyclopropanecarboxylic acid (a high affinity, partial agonist at strychnine-insensitive glycine receptors) resulted in a 3-fold increase in survival, a significant improvement in neurological status, and an extensive protection of vulnerable brain regions following severe forebrain ischaemia. A bolus of 1-aminocyclopropanecarboxylic acid 30 min prior to ischaemia did not further improve outcome compared to gerbils receiving their last injection 24 h prior to ischaemia. These findings are consistent with the hypothesis that chronic treatment with a glycine partial agonist desensitizes the N-methyl-D-aspartate receptor complex. Pharmacological intervention at the strychnine-insensitive glycine receptor may be an effective means of ameliorating the consequences of neuronal degeneration caused by excitotoxic phenomena.

The geometry of the adult canine proximal femur.

The canine is often used as a model to study functional bone adaptation after total hip replacement. To improve our understanding of the model, we defined the central tendencies and statistical variations in the cross-sectional geometry, angle of anteversion, and cervicodiaphyseal angle of the proximal femur in 15 adult male mongrel dogs and compared the results with published reports of the human femur. Numerous similarities in the cross-sectional geometry of the canine and the human femur were noted, supporting the use of the canine as a model. The two species differed in that the orientation of the principal axes in the proximal cross sections was not related to the angle of anteversion in the canine femur, whereas these angles are related in humans. In addition, the canine medullary canal is larger than the human medullary canal relative to the external dimensions of the femur, and hence the canine has relatively thinner cortical bone. This difference in femoral cross-sectional geometry may explain, in part, why the canine provides an accentuated model of bone loss in hip arthroplasty experiments.