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To the Editor: We read with interest the article by Castilletti et al. that showed prolonged shedding of Oropouche virus (OROV) in various body fluids (1). In addition, the authors [...]

Introduction Evidence from many studies has indicated that lactoferrin (LF) is present in the female reproductive tract secretions (Shaw et al. 2007; Zumoffen et al. 2013). It is known that [...], Since our previous results suggest that lactoferrin (LF) might have roles in the reproductive process and that its levels might change in the female tract as a response to various factors, the aim of this investigation was to assess whether LF levels in cervical secretions correlate with reproductive parameters from in vitro fertilization (IVF) patients. Cervical fluid samples were obtained from 34 women under 40 years old enrolled for assisted reproduction techniques, and LF concentration was measured. The mean total protein concentration in all cervical fluid samples was 842.8 6 116.9 lg/mL. The mean concentration of LF was 0.73 6 0.06 ng LF/lg of total proteins. We observed that higher LF levels in cervical fluid correlated with lower IVF rates when all patients were analyzed; this negative correlation was also sustained when only patients [greater than or equal to]35 years were studied. The mean LF concentration in cervical fluid was significantly lower among patients with normal IVF rates than in those with values 50% or less. Using a LF cutoff value of 0.83 ng/lg of total proteins, the study revealed a significant association between the LF levels below 0.83 ng/lg of total proteins and IVF rates above 50%. LF levels in cervical mucus could potentially be used as a marker of fertilization outcome. Key words: lactoferrin, in vitro fertilization, outcome, cervical fluid. Puisque les resultats obtenus precedemment par les auteurs suggerent que la LF pourrait jouer un role dans le processus de reproduction et que ses niveaux pourraient changer dans les voies genitales feminines en reponse a divers facteurs, l'objectif de cette etude consistait a evaluer si les niveaux de LF des secretions cervicales sont correles avec les parametres reproducteurs de patientes ayant subi une fecondation in vitro (FIV). Des echantillons de liquide cervical ont ete obtenus de 34 femmes de moins de 40 ans inscrites a un protocole de procreation assistee et la concentration de LF a ete mesuree. La concentration moyenne de proteines totales dans tous les echantillons de liquide cervical etait de 842,8 6 116,9 lg/mL. La concentration moyenne de LF etait de 0,73 60,06 ng LF/lg de proteines totales. Les auteurs ont observe que des niveaux plus eleves de LF dans le liquide cervical etaient correles avec des taux de FIV plus faibles lorsque les donnees de toutes les patientes etaient analysees; cette correlation negative etait egalement maintenue lorsque seules les patientes de 35 ans et moins etaient etudiees. La concentration moyenne de LF du liquide cervical etait significativement plus faible chez les patients presentant des taux de FIV normaux que chez celles dont les taux etaient de 50 % et moins. En utilisant une valeur seuil de LF de 0,83 ng LF/lg de proteines totales, cette etude a revele une association significative entre les niveaux de LF inferieurs a 0,83 ng LF/lg de proteines totales et des taux de FIV superieurs a 50 %. Les niveaux de LF dans le mucus cervical pourraient potentiellement etre utilises comme marqueur du resultat de la fecondation. [Traduit par la Redaction] Mots-cles : lactoferrine, fecondation in vitro, resultat, liquide cervical.

Author(s): Wei Gu [sup.1] [sup.2] , Xianding Deng [sup.1] [sup.2] , Marco Lee [sup.3] , Yasemin D. Sucu [sup.1] [sup.2] , Shaun Arevalo [sup.1] [sup.2] , Doug Stryke [sup.1] [sup.2] [...], We developed a metagenomic next-generation sequencing (mNGS) test using cell-free DNA from body fluids to identify pathogens. The performance of mNGS testing of 182 body fluids from 160 patients with acute illness was evaluated using two sequencing platforms in comparison to microbiological testing using culture, 16S bacterial PCR and/or 28S-internal transcribed ribosomal gene spacer (28S-ITS) fungal PCR. Test sensitivity and specificity of detection were 79 and 91% for bacteria and 91 and 89% for fungi, respectively, by Illumina sequencing; and 75 and 81% for bacteria and 91 and 100% for fungi, respectively, by nanopore sequencing. In a case series of 12 patients with culture/PCR-negative body fluids but for whom an infectious diagnosis was ultimately established, seven (58%) were mNGS positive. Real-time computational analysis enabled pathogen identification by nanopore sequencing in a median 50-min sequencing and 6-h sample-to-answer time. Rapid mNGS testing is a promising tool for diagnosis of unknown infections from body fluids. A universal method enables high-specificity, unbiased pathogen detection from diverse body fluids using metagenomic sequencing and may accelerate clinical decisions.

The aim of this study was to elucidate the interactive effect of central hypovolemia and plasma hyperosmolality on regulation of peripheral vascular response and AVP secretion during heat stress. Seven male subjects were infused with either isotonic (0.9%; NOSM) or hypertonic (3.0%; HOSM) NaC1 solution and then heated by perfusing 42[degrees]C (heat stress; HT) or 34.5[degrees]C water (normothermia; NT) through water perfusion suits. Sixty minutes later, subjects were exposed to progressive lower body negative pressure (LBNP) to -40 mmHg. Plasma osmolality ([P.sub.osmol]) increased by ~11 mosmol/kg[H.sub.2]O in HOSM conditions. The increase in esophageal temperature before LBNP was much larger in HT-HOSM (0.90 [+ or -] 0.09[degrees]C) than in HT-NOSM (0.30 [+ or -] 0.07[degrees]C) (P < 0.01) because of osmotic inhibition of therrnoregulation. During LBNP, mean arterial pressure was well maintained, and changes in thoracic impedance and stroke volume were similar in all conditions. Forearm vascular conductance (FVC) before application of LBNP was higher in HT than in NT conditions (P < 0.001) and was not influenced by [P.sub.osmol] within the thermal conditions. The reduction in FVC at -40 mmHg in HT-HOSM (-9.99 [+ or -] 0.96 units; 58.8 [+ or -] 4.1%) was significantly larger than in HT-NOSM (-6.02 [+ or -] 1.23 units; 44.7 [+ or -] 8.1%) (P < 0.05), whereas the FVC response was not different between NT-NOSM and NT-HOSM. Plasma AVP response to LBNP did not interact with [P.sub.osmol] in either NT or HT conditions. These data indicate that there apparently exists an interactive effect of [P.sub.osmol] and central hypovolemia on the peripheral vascular response during heat stress, or peripheral vasodilated conditions, but not in normothermia. plasma osmolality; baroreflexes; forearm vascular conductance; lower body negative pressure; arginine vasopressin

The subfornical organ (SFO), median preoptic nucleus (MnPO), and organum vasculosum lamina terminalis (OVLT), which are associated with the lamina terminalis, are important in the control of body fluid balance. Neurons in these regions express estrogen receptor (ER)-[alpha], but whether the ER-[alpha] neurons are activated by hypertonicity and whether hypertonicity regulates ER-[alpha] expression are not known. Using fluorescent, double-label immunocytochemistry, we examined the expression of ER-[alpha]-immunoreactivity (ir) and Fos-ir in control and water-deprived male rats. In control animals, numerous ER-[alpha]-positive neurons were expressed in the periphery of the SFO, in both the dorsal and ventral MnPO, and in the dorsal cap of the OVLT. Fos-positive neurons were sparse in euhydrated rats but were numerous in the SFO, MnPO, and the dorsal cap of the OVLT after 48-h water deprivation. Most ER-[alpha]-ir neurons in these areas were positive for Fos, indicating a significant degree of colocafization. To examine the effect of dehydration on ER-[alpha] expression, animals with and without lesions surrounding the anterior and ventral portion of the 3rd ventricle (AV3V) were water deprived for 48 h. Water deprivation resulted in a moderate increase in ER-[alpha]-ir in the SFO of sham-lesioned rats (P = 0.03) and a dramatic elevation in AV3V-lesioned animals (P < 0.05). This was probably induced by the significant increase in plasma osmolality in both dehydrated groups (P < 0.001) rather than a decrease in blood volume, because hematocrit was significantly increased only in the dehydrated sham-lesioned animals. Thus these studies implicate the osmosensitive regions of the lamina terminalis as possible targets for sex steroid effects on body fluid homeostasis. anteroventral third ventricle; Fos; organum vasculosum lamina terminalis; oxytocin; subfornical organ; water deprivation

The mechanism by which lactating rats increase fluid consumption to meet the demands of milk production is unknown. Because ANG II is the most potent dipsogenic stimulus known, this study examined whether angiotensinergic signaling plays a role in enhanced drinking in lactating rats. ANG II administered intracerebroventricularly caused a significantly greater dipsogenic response in lactating rats than in control rats, suggesting that dipsogenic responsivity to ANG II is enhanced in the brains of lactating rats. The angiotensin type 1 ([AT.sub.1]) ANG II receptor subtype antagonist SKF-108566, also given intracerebroventricularly, caused a significant reduction in water consumption in lactating rats, whereas it did not significantly affect water intake in control rats. In contrast, stimulation of drinking by the muscarinic agonist carbachol, also administered intracerebroventricularly, did not differ between lactating and control rats. Inhibition of drinking by the muscarinic antagonist atropine also did not differ significantly between lactating and control rats. These results suggest that the increased drinking in lactating rats involves an increased responsivity to ANG II in neurons that mediate dipsogenesis, as well as an enhancement in the amount of angiotensinergic input to these ANG II-responsive neurons. dipsogenesis; angiotensin II; atropine; isoproterenol; food intake

Byline: Malcolm A. Holliday (1) Keywords: Key wordsaHistory; Fluid therapy; Body fluid physiology; Extracellular fluid; Potassium; James Gamble; Daniel Darrow Abstract: The development of body fluid physiology and fluid therapy in pediatrics has special importance in the history of medicine because this development introduced physiology into clinical practice. James Gamble and Dan Darrow were leaders in this enterprise. Gamble was part of the group John Howland attracted to Johns Hopkins to establish the first organized program for clinical investigators in pediatrics. This group initiated fluid therapy as effective treatment for diarrheal dehydration and, led by Gamble, developed the discipline of body fluid physiology. Gamble was the first to describe the nature of extracellular fluid (ECF) to clinicians, using the new terminology for characterizing electrolytes in solution. In doing so, he became the teacher of body fluid physiology to a generation of medical students. Inexplicably, in his later years he failed to adopt yet newer terminology defining cations, anions, and acid-base status. This failure compromised his legacy. Dan Darrow extended our understanding of how body fluids react to hyper- and hyponatremia and to potassium deficiency. He was the first to add potassium to parenteral fluid therapy. In doing so, he broadened clinicians&apos; understanding of body fluids but changed the emphasis of fluid therapy from rapid ECF restoration to replacement of estimated deficits. Unfortunately, this change in concept, taught by his successors as deficit therapy, slowed the adoption of oral rehydration therapy for treating diarrheal dehydration. The lapses noted for each of these men, now seen in hindsight, pale in comparison to their contributions. Pediatrics, medicine, and surgery are all indebted to the research of each, which emphasized the value of basic physiology in clinical practice. Author Affiliation: (1) Department of Pediatrics, University of California San Francisco, Box 648, Inverness, CA 94937, USA e-mail: mah@itsa.ucsf.edu Tel.: +1-415-669-1422, Fax: +1-415-669-1719, US Article note: Received: 18 April 2000 / Accepted: 16 May 2000

Pseudohypoaldosteronism appears to cause excess fluid in the lungs and respiratory system. Pseudohypoaldosteronism is characterized by abnormal sodium transport in the body. In a study of 9 patients with pseudohypoaldosteronism, mutations were found in the genes for parts of the sodium channel, which transports sodium across tissues. The patients had more than twice as much fluid in their respiratory system as a healthy person would have. Most had chest congestion, coughing and wheezing. This illustrates the role that sodium plays in keeping fluid levels in the respiratory system normal.

Although it has been known for decades that the tight junctions of fluid-transporting epithelia are leaky to ions, it has not been possible to determine directly whether significant transjunctional water movement also occurs. An optical microscopic technique was developed for the direct visualization of the flow velocity profiles within the lateral intercellular spaces of a fluid-absorptive, cultured renal epithelium (MDCK) and used to determine the velocity of the fluid flow across the tight junction. The flow velocity within the lateral intercellular spaces fell to near zero adjacent to the tight junction, showing that significant transjunctional flow did not occur, even when transepithelial fluid movement was augmented by imposition of osmotic gradients.

Intrarenal control mechanisms play an important role in the maintenance of body fluid and electrolyte balance and pH homeostasis. Recent discoveries of new ion transport and regulatory pathways in the [...]

Hypertonic saline solutions maintain equal levels of plasma volume, extracellular fluid volume (ECFV), and interstitial fluid volume (ISFV) in intact animals. The fluid shifts may be responsible for hemorrhagic post-resuscitation organ failure and differ with the resuscitation solutions: normal saline, hyperoncotic saline (HA), hypertonic saline (HS) or a mix of HA and HS. More fluid is required for normal saline than any other solution and the resuscitation is slow. The hypertonic saline solution and the mixture normalize cellular volume in lung, skin and muscle. The results of a study on hemorrhaged rats are discussed.

Exogenous serotonin (5-HT) increases the gastric acid response activated by microinjection of a stable thyrotropin releasing hormone (TRH) analogue in the dorsal vagal complex (DVC) of rats. Results of a study indicate that a receptor belonging to 5HT2 family is responsible for mediation in 5-HT action. A promoting interaction was also observed between endogenous TRH and 5-HT in DVC at the 5-HT2 receptors in the gastric acid response to excitation of Rpa neurons.

A study of the involvement of plasma factors of one kidney, one clip (1K,1C) hypertension in smooth muscle cell growth enhancement in rats reveals that growth enhancement depends on the concentration of humoral factors and that these factors respond to boiling but oppose charcoal absorption and proteolysis. Smooth muscle cell growth is increased differentially by plasma-derived serum (PDS) from 1K,1C rats. Aortic and arteriolar cells exhibit similar levels of differential growth due to PDS, indicating the involvement of the same factors in the growth of both cells.

A study of platelet-free plasma-derived serum (PDS) from rats with one-kidney one clip hypertension to evaluate the role of humoral factors in hypertension reveals that plasma factors differentially stimulate c-fos-mRNA expression, thymidine incorporation and abnormal proliferation of aortic smooth muscle cells. Humoral factors include catecholamines, natriuretic factors, norepinephrine and angiotensin II. Differential effects of humoral factors arise due to reduced levels of growth inhibitors and growth promoting factor stimulation.

Tetanus toxoid (TT) antigen-induced anti-tetanus toxoid antibody (anti-TT) synthesis in older and younger rats is comparatively analyzed for characterization of humoral immunity responses in elder populations. Lymphocytes isolated from older rats exhibit a low yield of anti-TT product in contrast to anti-TT synthesized in lymphocytes of younger rats. Attenuation of anti-TT synthesis in older rats is ascribed to a reduced number of B cells releasing the anti-TT immunoglobin (IgG) which renders a decline in the average levels of anti-TT IgG synthesized per TT-selective B cell. Serum titers in immunized young rats is markedly enhanced, while that in older rats exhibits a decline.

The effect of endogenous angiotensin II on the increase in hematocrit induced by atrial natriuretic peptide (ANP) was examined on nephrectomized rats. Endogenous angiotensin II modulated the effect of ANP on vascular permeability. This was attributed to the supression of angiotensin II generation and antagonism of its receptors which abolishes the effect of ANP on hematocrit. The result suggests a possible role for tissue renin-angiotensin interaction in controlling endogenous ANP on transcapillary shift and formation of edema.

Apolipoprotein J (apoJ) is an ubiquitous protein thought to play roles in lipid transport, sperm maturation, regulation of complement, apoptosis and membrane recycling. In situ hybridization analysis was conducted to localize the sites of apoJ synthesis. The results showed that apoJ synthesis is restricted to epithelial and other secretory cells in diverse tissues. It is proposed that apoJ functions to stabilize cell membranes at different fluid-tissue interfaces.

The arterial pressure of the adult human rarely deviates from normal by more than 10 to 15 percent during each day. To achieve such constancy, the body has a network [...]

Abstract: The main objective of this study was to evaluate whether daily consumption of caffeine-containing beverages is related to the prevalence and severity of premenstrual syndrome apart from any effects of daily total fluid consumption. A secondary objective was to determine whether daily total fluid consumption itself is related to premenstrual syndrome. The study is based on 841 responses to a questionnaire probing menstrual and premenstrual health, and daily fluid consumption, which was mailed to female university students in Oregon. Analysis of the data revealed that consumption of caffeine-containing beverages was strongly related to the prevalence of premenstrual syndrome. Among women with more severe symptoms, the relation between consumption of caffeinecontaining beverages and premenstrual syndrome was dose-dependent, with prevalence odds ratios equal to 1.3 for consumers of one cup of a caffeine-containing beverage per day and increasing steadily to 7.0 for consumers of eight to 10 cups per day. The effects were apparent among both caffeine-containing tea/coffee consumers and caffeine-containing soda consumers. The observed effects were only slightly reduced when daily total fluid consumption was controlled. Daily total fluid consumption also was related to the prevalence of premenstrual symptoms although the effects were large only for consumers of 13-19 cups of fluid per day (the largest amount studied). (Am J Public Health 1990; 80:1106-1110.), Studies show that the consumption of caffeine-containing beverages is associated with the development and worsening of the symptoms of premenstrual syndrome (PMS). This syndrome occurs several days before the onset of menstruation, and may be associated with irritability, emotional tension, anxiety, mood changes, depression, headache, breast tenderness with swelling, and water retention. These symptoms usually decrease in severity towards the onset of menstruation. Triggers of PMS other than caffeine include alcohol and cigarette use, lack of exercise, oral contraceptive treatment, and diets high in beef and refined sugar products. Caffeine may affect daily total fluid consumption, which influences the development of PMS. The relation between PMS and caffeine-containing beverage intake and total fluid intake was assessed. A questionnaire evaluating menstrual and premenstrual health and daily fluid consumption was completed by 841 female university students in Oregon. The results showed that consumption of caffeine-containing beverages was associated with an increase in the prevalence of PMS. Increasing doses of caffeine, as indicated by number of cups of caffeine-containing beverages consumed per day, was associated with an increased prevalence and severity of PMS. These effects occurred with tea, coffee, and caffeine-containing soda, and declined when daily total fluid consumption was controlled. Increased daily total fluid consumption was also associated with prevalence of PMS, but effects only became significant when 13 to 19 cups of fluid per day were consumed. (Consumer Summary produced by Reliance Medical Information, Inc.)

Young people with insulin dependent diabetes mellitus are three times more likely to die in childhood than the general population. (1) Despite advances in management over the past 20 years, [...]

Context.--Differentiating reactive effusion, malignant mesothelioma, and metastatic adenocarcinoma in body cavity fluids can be challenging. Interpreting immunohistochemical markers in cell block preparations can be difficult because of nonspecific staining, focal staining, or poor staining quality. We selected a panel of conventional and newer markers to assess their utility in evaluating effusions. Objective.--To evaluate the efficacy of 5 immunohistochemical markers in the differential diagnosis of reactive mesothelial proliferation, malignant mesothelioma, and metastatic adenocarcinoma in body cavity fluids. Design.--A total of 72 formalin-fixed, paraffin-embedded cell block specimens from pleural and peritoneal effusions, including 5 mesotheliomas, 48 adenocarcinomas, and 19 benign effusions were stained with antibodies against calretinin, D2-40, XIAP, MOC-31, and WT1. Results.--All benign effusions and mesotheliomas demonstrated diffuse membranous staining with D2-40. All mesotheliomas displayed calretinin positivity, whereas only 58% of benign effusions stained focally with calretinin. MOC-31 was positive in all cases of adenocarcinoma, whereas all benign effusions and mesotheliomas were negative. All cases of the metastatic adenocarcinoma were negative for calretinin and D2-40. However, background reactive mesothelial cells were positive for calretinin and D2-40. Overall, D2-40 highlighted more mesothelial cells than calretinin. WT1 was positive in 50% of benign effusions, 60% of mesotheliomas, and 27% of adenocarcinomas. XIAP stained most mesotheliomas (80%), some adenocarcinomas (51%), and rare benign effusions (11%). Conclusions.--MOC-31 and D2-40 were very sensitive and specific markers of epithelial and mesothelial cells, respectively. Compared with calretinin, D2-40 was a more sensitive marker of mesothelial cells. WT1 proved to be nonspecific. XIAP was not a sensitive marker for malignancy and had a limited value in cytology. We recommend using a panel to include MOC-31 and D2-40 to improve diagnostic accuracy in body cavity effusions., One of the diagnostic challenges of evaluating body cavity fluids is to distinguish reactive mesothelial cells from malignant mesothelioma and metastatic adenocarcinoma. Various mesothelial and epithelial immunohistochemical markers are currently [...]

The airway surface liquid (ASL) is the thin layer of fluid coating the luminal surface of airway epithelial cells at an air interface. Its composition and osmolality are thought to be important in normal airway physiology and in airway diseases such as asthma and cystic fibrosis. The determinants of ASL osmolality include epithelial cell solute and water transport properties, evaporative water loss, and the composition of secreted fluids. We developed a noninvasive approach to measure ASL osmolality using osmotically sensitive 400-nm-diam liposomes composed of phosphatidylcholine/cholesterol/polyethylene glycol-phosphatidylcholine (1:0.3:0.08 molar ratio). Calcein was encapsulated in the liposomes at self-quenching concentrations (30 mM) as a volume-sensitive marker, together with sulforhodamine 101 (2 mM) as a volume-insensitive reference. Liposome calcein/sulforhodamine 101 fluorescence ratios responded rapidly ([is less than] 0.2 s) and stably to changes in solution osmolality. ASL osmolality was determined from calcein/sulforhodamine 101 fluorescence ratios after addition of microliter quantities of liposome suspensions to the ASL. In bovine airway epithelial cells cultured on porous supports at an air-liquid interface, ASL thickness (by confocal microscopy) was 22 [micro]m and osmolality was 325 [+ or -] 12 mOsm. In anesthetized mice in which a transparent window was created in the trachea, ASL thickness was 55 [micro]m and osmolality was 330 [+ or -] 36 mOsm. ASL osmolality was not affected by pharmacological inhibition of CFTR in airway cell cultures or by genetic deletion of CFTR in knockout mice. ASL osmolality could be increased substantially to [is greater than] 400 mOsm by exposure of the epithelium to dry air; the data were modeled mathematically using measured rates of osmosis and evaporative water loss. These results establish a ratio imaging method to map osmolality in biological compartments. ASL fluid is approximately isosmolar under normal physiological conditions, but can become hyperosmolar when exposed to dry air, which may induce cough and airway reactivity in some patients. KEY WORDS: water permeability * cystic fibrosis * fluorescence self-quenching * trachea * CFTR

Adequate body and vocal fold hydration are believed to be critical to phonation. We hypothesized that body fluid reduction, without dehydration, would increase phonation threshold pressure ([P.sub.th]) and be associated with patient-perceived increases in phonatory effort and worsening voice quality. Using a single-subject, full-reversal design, a controlled volume of body fluid was repeatedly removed via ultrafiltration from adults with end stage renal disease (2 women, 4 men, ages 40-85 yrs). Two additional men (ages 81 and 68 yrs) served as placebo and healthy true controls, respectively. [P.sub.th], vocal effort and quality, blood pressure, and heart rate were assessed longitudinally. [P.sub.th] increased significantly with fluid volume reduction (3-4% of body weight from a hypervolemic to a grossly normovolemic body state) and reversed to baseline with fluid replacement in 4 of 6 treated subjects. Effects were observed with net ultrafiltration rates greater than or equal to 1.0 L/h; these effects were not observed in control subjects. Fluid loss accounted for 31.6% of variance in [P.sub.th] and 40.0% of variance in perceived vocal effort. Heart rate, systolic blood pressure, and/or diastolic blood pressure were significantly correlated with [P.sub.th] or fluid volume reduction in 6 subjects, including the placebo control (-.70 [is less than or equal to] r [is greater than or equal to] -.44). Results indicate that substantial extracellular volume depletion without body dehydration causes voice symptoms, an effect possibly mediated by autonomic nervous control. We propose that mechanisms intrinsic to the vocal fold regulate its water flux and respond to hydration challenges. KEY WORDS: voice disorders, hydration, water transport, larynx, laryngeal physiology, Clinicians and vocalists believe that voice is best produced in a well-hydrated body state. Systemic dehydration by drugs, disease, and reduced water ingestion are thought to contribute to voice disorders. [...]

Although it is well accepted that bone tissue metabolism is regulated by external mechanical loads, it remains unclear to what load-induced physical signals bone cells respond. In this study, a novel computer-controlled stretch device and parallel plate flow chamber were employed to investigate cytosolic calcium [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] mobilization in response to a range of dynamic substrate strain levels (0.1-10 percent, 1 Hz) and oscillating fluid flow (2 N/[m.sup.2], 1 Hz). In addition, we quantified the effect of dynamic substrate strain and oscillating fluid flow on the expression of mRNA for the bone matrix protein osteopontin (OPN). Our data demonstrate that continuum strain levels observed for routine physical activities ([is less than] 0.5 percent) do not induce [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] responses in osteoblastic cells in vitro. However, there was a significant increase in the number of responding cells at larger strain levels. Moreover, we found no change in osteopontin mRNA level in response to 0.5 percent strain at 1 Hz. In contrast, oscillating fluid flow predicted to occur in the lacunar-canalicular system due to routine physical activities (2 N/[m.sup.2], 1 Hz) caused significant increases in both [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] and OPN mRNA. These data suggest that, relative to fluid flow, substrate deformation may play less of a role in bone cell mechanotransduction associated with bone adaptation to routine loads. [S0148-0731(00)01204-8]